Hypertonic antimicrobial therapeutic compositions

ABSTRACT

Therapeutic compositions, primarily for topical application, and methods of making and using the composition. Pharmaceutical compositions formulated for specific forms of administration are also provided.

CROSS REFERENCE TO RELATED APPLICATION

This application claims the benefit of priority under 35 U.S.C. §119(e)to U.S. Provisional Patent Application Ser. No. 61/876,524, filed Sep.11, 2013, which is incorporated herein by reference.

FIELD OF THE INVENTION

This invention relates to a composition and methods with broadantimicrobial activity against bacteria, fungi, viruses, and protozoans.The composition and methods can be used in the prevention and treatmentof pathogenic processes in mammals, e.g., humans and animals, includinglivestock or pets, by any administration method, but is preferablyapplied topically.

BACKGROUND OF THE INVENTION

New regulatory measures, as well as the appearance of microbialresistance to available antibiotics, have increased the search foralternative solutions, particularly those providing effective treatmentwith low risk of inducing resistance.

Resistance to antibiotics has become a public health matter and hasincreased the cost of treatment. Therefore, the development of acomposition with antimicrobial activity that does not pose resistanceand toxicity problems is advantageous to animal and human health.

Thus, the inventors have developed the compositions disclosed herein toaddress the objectives of: providing a safe and effective compositionadministrable to an animal or human suffering from a condition caused bya microbial infestation or infection; minimizing side effects or tissueresidues resulting from administration of the composition; providing acomposition effective against a broad range of pathogens, including butnot limited to, bacteria, viruses, fungi, or protozoans; and providing acomposition that can be easily produced and at a reasonable cost; andall of the above with concomitant pain relief or pain reduction.

Other objectives and applications of the subject invention will becomereadily apparent to a person of ordinary skill in the art in view ofthis disclosure provided in the subject specification and drawings.

SUMMARY OF THE INVENTION

The subject invention concerns an antimicrobial composition that can beadministered or topically applied to humans or other animals, providinga preventive, microbiostatic, or microbiocidal effect against a widerange of pathogenic microbes, including but not limited to, bacteria,viruses, fungi, and protozoans. Preferably, the composition isformulated as a liquid or paste useful as a topical dressing or rinseapplied or administered to wounds caused by injury or surgicalprocedures.

Advantageously, the composition can further promote wound healing and,unexpectedly, further provides pain reduction, or pain relief, which canreduce the amount of other potentially harmful or addictive painmedication.

The composition comprises a mixture of ingredients which can be easilyobtained or prepared. The composition has a long shelf life and is notknown to induce resistance in the target pathogen. The composition canbe applied or administered at strengths which are highly effective, yetsafe to a patient in need of treatment using the composition.

A preferred embodiment of the invention comprises an antiseptic, e.g.,chlorhexidine, an antimicrobial, e.g., chloramine T, and a peroxide, andone or more salts, such as sodium bicarbonate, potassium bicarbonate,sodium chloride, and the like. Chlorhexidine is commercially availableas chlorhexidine gluconate (4% w/v) gluconolactone, and is oftencombined with ingredients such as poloxamer, isopropyl alcohol,lauramine oxide (surfactant), herbacol (fragrance), and colorant, (suchas FD&C red) in water. Accordingly, a preparation of the subjectinvention can also comprise these ingredients.

The subject invention can be formulated as a concentrate, e.g., as apaste, gel, or ointment, or can be diluted using an aqueous orwater-miscible solvent to be administered as a rinse. In either form,the composition can be administered directly to a wound area, topicallyor by subcutaneous injection, or can be incorporated onto or into awound dressing material such as a bandage, patch, or suture material.

The composition of the invention can be, but is not limited to, use inthe following applications:

-   -   1) Mouth rinse for antimicrobial gargle/sinus, rinse        antibacterial/viral;    -   2) surgical rinse to decontaminate wounds;    -   3) surgical rinse to create pain killer in surgical sites;    -   4) paste (concentrate);    -   5) act as antimicrobial action/pre opp.wound/mouth/sinus        cleanse;    -   6) use on washing hands/body before surgery, or for routine        care;    -   7) act as surgical treatment to increase or potentiate healing        in wounds;    -   8) act as an agent to create pain killer in wounds by turning        local anesthetic into anesthetic bicarbonate/analgesic for        post-op pain control, or inhibit pain cascade in surgical/burn        wounds;    -   9) turn a contaminated wound into a non-contaminated wound;    -   10) as a wound debridement;    -   11) to reduce or remove infections from skin, e.g.,        acne/rosacea;    -   12) insect bites, removes sting/neutralizes poison;    -   13) use for diabetic ulcerations/poor wound healing;    -   14) promote angiogenesis and tissue growth;    -   15) chemical/heat related burns;    -   16) treat resistant pathogenic microbial infections, e.g., MRSA,        and the like;    -   17) treat traumatic injuries (war etc.), to decontaminate wounds        and potentiate healing and reduce pain of trauma;    -   18) treat orthopedic injuries, surgeries and repairs in human or        animal, including treatment and impregnation of orthopedic        implants and hardware; and,    -   19) add to wound dressings or plugs (e.g., collagen plugs for        dental extraction sites).

One aspect of the invention is a therapeutic composition comprising achloride salt; a source of bicarbonate; a source of hypochlorite; and,an antimicrobial agent selected from biguanids, triguanides,bisbiguanides and analogs thereof; wherein the amount of the salt in thecomposition is sufficient to render the composition hypertonic, andwherein the composition is alkaline. In certain embodiments, thechloride salt is selected from sodium chloride and potassium chloride.In certain embodiments, the concentration of the chloride salt is atleast 200 mM. In certain embodiments, the concentration of the chloridesalt is in the range of about 4 molar to about 8 molar. In certainembodiments, the concentration of the chloride salt is in the range ofabout 5 molar to about 7 molar. In other embodiments, the concentrationof the chloride salt is at least about 5 molar. In other embodiments,the concentration of the chloride salt is no greater than about 7 molar.In specific embodiments, the concentration of the chloride salt is about6.8 molar. In certain embodiments, the concentration of the chloridesalt is in the range of about 30% (w/v) to about 40% (w/v).

In certain embodiments, the source of bicarbonate is a bicarbonate salt.In specific embodiments, the bicarbonate salt is selected from the groupconsisting of sodium bicarbonate, calcium bicarbonate, potassiumbicarbonate and ammonium bicarbonate. In certain embodiments, theconcentration of the carbonate salt is in the range of about 70% toabout 95% (w/v). In some embodiments, the concentration of the carbonatesalt is in the range of about 8 molar to about 11 molar. In certainembodiments, the source of carbonate provides a concentration ofcarbonate in the range of about 4.9 molar to about 6.5 molar.

In certain embodiments, the concentration of the source of hypochloritein the composition is about 0.5% to about 5% (w/v). In some embodiments,the concentration of the source of hypochlorite in the composition is atleast 0.5% (w/v). In specific embodiments, the source of hypochlorite istosylchloramide (N-chloro-tosylamide).

In some embodiments, the concentration of the antimicrobial agent in thecomposition is in a range of about 0.12% to about 6% (v/v). In someembodiments, the concentration of antimicrobial in the composition is ina range of about 1.2% to about 2% (v/v). In certain embodiments, theantimicrobial agent is a bisbiguanidine. In specific embodiments, thesource of bisbiguanide is chlorhexidine gluconate.

In some embodiments, the therapeutic compositions additionally include acompound that provides oxygen. In these embodiments, the oxygenproducing compound is peroxide. In these embodiments, the source ofperoxide is selected from the group consisting of hydrogen peroxide,carbamide peroxide and sodium percarbonate. In certain embodiments, theconcentration of the oxygen producing compound in the composition is inthe range of about 0.1% to about 1% (v/v). In specific embodiments, theconcentration of oxygen-producing compound in the composition is about1% (v/v).

In certain embodiments, the therapeutic compositions additionallyinclude a poloxamer. In certain embodiments, the concentration ofpoloxamer in the composition is in the range of about 6% to about 12%(w/v). In certain embodiments, the concentration of poloxamer in thecomposition is at least about 6%. In specific embodiments, the poloxameris poloxamer 237.

In certain embodiments, the therapeutic compositions additionallyinclude a surfactant. In certain embodiments, the surfactant is anamphoteric surfactant. In certain embodiments, the surfactant is anamine oxide. In certain embodiments, the concentration of surfactant inthe composition is in the range of about 0.1% to about 1% (w/v). Incertain embodiments, the concentration of surfactant in the compositionis in the range of about 0.2% to about 0.5% (w/v). In specificembodiments, the surfactant is lauramine oxide (N,N-DimethyldodecylamineN-oxide).

In certain embodiments, the therapeutic composition additionallyincludes a compound selected from the group consisting of ananti-microbial compound, an anti-viral compound and an anti-fungalcompound.

In certain embodiments, the pH of the composition is greater than 7. Insome embodiments, the pH of the composition is in the range of about 7.2to about 7.8.

In certain embodiments, the therapeutic compositions additionallyinclude a gluconolactone. In certain embodiments, the concentration ofgluconolactone in the composition is in the range of about 0.1% to about% (w/v). In specific embodiments, the concentration of gluconolactone inthe composition is at least about 0.9% (w/v).

A related aspect of the invention is a therapeutic composition includinga salt selected from the group consisting of sodium chloride andpotassium chloride; a source of carbonate selected from the groupconsisting of sodium bicarbonate, potassium bicarbonate, calciumbicarbonate and ammonium bicarbonate; a source of peroxide selected fromhydrogen peroxide, carbamide peroxide and sodium percarbonate; N-chlorotosylamide; and chlorhexidine; wherein the amount of the salt in thecomposition is sufficient to render the composition hypertonic, andwherein the composition is alkaline.

A related aspect of the invention is a therapeutic composition includinga salt selected from the group consisting of sodium chloride andpotassium chloride; a source of carbonate selected from the groupconsisting of sodium bicarbonate, potassium bicarbonate, calciumbicarbonate and ammonium bicarbonate; a source of peroxide selected fromhydrogen peroxide, carbamide peroxide and sodium percarbonate; N-chlorotosylamide; and chlorhexidine; wherein the amount of the salt in thecomposition is sufficient to render the composition hypertonic, andwherein the composition is alkaline.

Another aspect of the invention is a scaffolding material containing acomposition of the present material. Such scaffolding material can be abiomaterial scaffold or a synthetic scaffold. Such scaffolds include,but are not limited to, collagen plugs, or equivalents, vascular woundrepair devices, hemostatic dressings, patches and glues, sutures, drugdelivery and in tissue engineering applications, such as, for example,scaffolding, ligament prosthetic devices and in products for long-termor bio-degradable implantation into the human body.

Another aspect of the invention is a method of treating a disease ordisorder or injury in a mammal comprising administering a therapeuticcomposition to the mammal. In one embodiment, a therapeutic compositionof this disclosure is administered to treat a wound, treat a bacterialinfection, treat a viral infection, treat a fungal infection, reduceinflammation, promote angiogenesis, promote tissue growth or reducepain.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Exemplary formulation of a paste and rinse of the presentinvention. Percentage of each ingredient listed as weight/volume (w/v)(with the exception of hydrogen peroxide).

FIG. 2. Exemplary formulation of a paste and rinse of the presentinvention. Percentage of each ingredient listed as weight/weight (w/w).

FIG. 3. Effect of a paste of the present invention on a pre-cancerouslesion of the lower lip. (A) Picture of the lesion prior to treatment;(B) paste of the present invention applied to lesion; (C) lower lip at27 days post-treatment.

FIG. 4. Effect treating an oral pre-cancer with a composition of thepresent invention. (A) Picture of the lesions on the tongue prior totreatment; (B) view of the tongue at 27 days post-treatment; (C) at 27days post-treatment.

FIG. 5. Treatment of scar tissue containing antibiotic-resistantbacteria using a paste of the present invention. (A) View of scar tissuelesion prior to treatment; (B) View of scar tissue lesion after 8 daysof treatment; (C)) View of scar tissue lesion after finishing oftreatment.

FIG. 6-1 through 6-3. Treatment of facial acne using a paste of thepresent invention. (A) facial skin prior to treatment (frontal view);(B) facial skin after a single application of paste (front view); (C)facial skin after a single application of paste (view of right side offace); (D) facial skin after a single application of paste (view of leftside of face).

FIGS. 7-1 and 7-2. Treatment of a burn resulting from hot wax using apaste of the present invention. (A) View of skin three-days after burn;(B) View of skin 8 days after burn and 5 days following treatment; (C)View of burn area one year after burn.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to compositions and formulations usefulfor preventing, inhibiting or ameliorating a microbial infestation orinfection in humans or other animals. The composition disclosed hereinexhibits preventive, microbiostatic, or microbiocidal effects against awide range of pathogenic microbes, including but not limited to,bacteria, viruses, fungi, and protozoans. The claimed compositions andformulations are also useful for reducing inflammation and pain. In thisregard, the present invention improves upon related methods disclosed bythe inventors in U.S. Pat. No. 8,828,452, U.S. Patent Publication No.2008/0292731, and International (PCT) Publication No. WO 2014/127367,the contents of which are incorporated herein by reference in theirentirety. Preferably, the composition or formulation is applied oradministered to wounds caused by injury or trauma, or following asurgical procedure. In various embodiments, the claimed composition orformulation can be administered or applied as a liquid or paste usefulas a topical dressing or rinse, such as a dental rinse.

Advantageously, the compositions and formulations of the presentinvention comprise a mixture of ingredients which can be easily obtainedor prepared. Before proceeding further, it should be noted that as usedherein, the terms composition and formulation can be usedinterchangeably. Compositions of the present invention have a long shelflife and are not known to induce resistance in the target pathogen.Moreover, compositions of the present invention can be applied oradministered at strengths which are highly effective, yet safe to apatient in need of treatment using the composition.

A composition or formulation of the present invention can generally beprepared by combining one or more salts that increase the tonicity ofthe composition, such as sodium chloride or potassium chloride, and thelike, a source of carbonate, such as sodium bicarbonate or potassiumbicarbonate, and the like, an antiseptic, e.g., chlorhexidine and anantimicrobial, e.g., chloramine T. In certain embodiments, a compositionof the present invention may also include one or more additionalingredients selected from the group consisting of an oxygen-producing, apoloxamer, a surfactant and a polyhydroxy acid. Formulations ofexemplary embodiments are summarized in the tables provided in FIG. 1and FIG. 2.

The subject invention may preferably be formulated as a concentrate,e.g., as a paste, gel, or ointment, that can be diluted using an aqueousor water-miscible solvent to produce a liquid formulation that can beadministered as a rinse or topical scrub. Preferred formulations of twodifferent embodiments of the present invention will now be disclosed.

Paste

As noted above, a therapeutic composition of the present invention canbe formulated as a paste. As used herein, paste refers to a semi-solidmixture having a consistency between a solid and a liquid. As such, itwill be appreciated that pastes are made from mixing one or more solidswith one or more liquids to produce a viscous composition.

In certain embodiments, a therapeutic composition of the presentinvention comprises at least one salt at a concentration sufficient torender the composition hypertonic. Any salt(s) capable of rendering thecomposition hypertonic can be used to produce a composition of thepresent invention, although preferred salts are chloride salts. Incertain embodiments, the at least one salt is selected from the groupconsisting of sodium chloride and potassium chloride. In certainembodiments, the concentration of salt in the composition is at least200 mM. In certain embodiments, a concentration of salt in a compositionof the present invention is in the range of from about 4 molar to about8 molar. As used herein, and with particular regard to concentrations,the term about means+/−5%. Thus, for example, about 4 molar refers to arange of 3.8 molar to 4.2 molar. In certain embodiments, theconcentration of salt in a composition of the present invention is inthe range of from about 5 molar to about 7 molar. In certainembodiments, the concentration of salt in a composition of the presentinvention is at least about 5 molar. In on embodiment, the concentrationof salt in a composition of the present invention is no greater thanabout 7 molar. In certain embodiments, the concentration of salt in acomposition of the present invention is about 6.8 molar.

It will be appreciated by those skilled in the art that in addition tomolarity, the concentration of salt can also be measured on a weight tovolume basis. In certain embodiments, the concentration of salt in acomposition of the present invention is in the range of about 30% (w/v)to about 40% (w/v). In certain embodiments, the concentration of salt ina composition of the present invention is at least about 30% (w/v). Incertain embodiments, the concentration of salt in a composition of thepresent invention is no greater than about 39% (w/v). In certainembodiments, the concentration of salt in a composition of the presentinvention is about 30% (w/v). In certain embodiments, the concentrationof the salt in a composition of the present invention is about 35%(w/v). In certain embodiments, the concentration of the salt in acomposition of the present invention is about 39% (w/v).

It will be appreciated by those skilled in the art that theconcentration of salt can also be measured on a weight to weight basis.Thus, in certain embodiments, the concentration of salt in a compositionof the present invention is in the range of from about 15% to about 30%(w/w/). In certain embodiments, the concentration of salt in acomposition of the present invention is in the range of from about 18%to about 25% (w/w). In certain embodiments, the concentration of salt ina composition of the present invention is at least about 19% (w/w). Incertain embodiments, the concentration of salt in a composition of thepresent invention is about 20%. In certain embodiments, theconcentration of salt in a composition of the present invention is about23%.

A therapeutic composition of the present invention further comprises asource of bicarbonate. Any source of bicarbonate can be used to producea therapeutic composition of the present invention as along as itprovides a sufficient amount of bicarbonate for the intended purpose.

In certain embodiments, the source of the bicarbonate is a bicarbonatesalt. In certain embodiments, the bicarbonate salt is selected from thegroup consisting of sodium bicarbonate, calcium bicarbonate, ammoniumbicarbonate and sodium percarbonate. In certain embodiments, theconcentration of bicarbonate salt in a composition of the presentinvention is in the range of from about 8 molar to about 11.5 molar. Incertain embodiments, the concentration of bicarbonate salt in acomposition of the present invention is in the range of from about 8.5molar to about 11 molar. In certain embodiments, the concentration ofbicarbonate salt in a composition of the present invention is at least 8molar. In certain embodiments, the concentration of bicarbonate salt ina composition of the present invention is at least 11 molar. In certainembodiments, the concentration of bicarbonate in a composition of thepresent invention is in the range of from about 4.9 molar to about 6.5molar. In certain embodiments, the concentration of bicarbonate in acomposition of the present invention is at least 5 molar.

In certain embodiments, the concentration of bicarbonate salt in acomposition of the present invention is in the range of from about 70%(w/v) to about 95% (w/v). In certain embodiments, the concentration ofbicarbonate salt in a composition of the present invention is in therange of from about 73% (w/v) to about 94% (w/v). In certainembodiments, the concentration of bicarbonate salt in a composition ofthe present invention is at least 73% (w/v). In certain embodiments, theconcentration of bicarbonate salt in a composition of the presentinvention is at least 93% (w/v). In certain embodiments, theconcentration of bicarbonate salt in a composition of the presentinvention is selected from about 73% (w/v) and about 93% (w/v).

In certain embodiments, the concentration of bicarbonate salt in acomposition of the present invention is in the range of from about 45%(w/w) to about 60% (w/w). In certain embodiments, the concentration ofbicarbonate salt in a composition of the present invention is in therange of from about 45% (w/w) to about 55% (w/w). In certainembodiments, the concentration of bicarbonate salt in a composition ofthe present invention is at least 45% (w/w). In certain embodiments, theconcentration of bicarbonate salt in a composition of the presentinvention is at least 55% (w/w). In certain embodiments, theconcentration of bicarbonate salt in a composition of the presentinvention is selected from about 46% (w/w) and about 55% (w/w).

In certain embodiments, the ratio of bicarbonate to salt is in the rangeof from about 1:1.3 to about 1:3. In certain embodiments, the ratio ofbicarbonate to salt is in the range of from about 1:1.3 to about 1:2.5.In certain embodiments, the ratio of bicarbonate to salt is about 1:2.3.In certain embodiments, the ratio of bicarbonate to salt is about 1:2.5.

A therapeutic composition of the present invention further comprises asource of hypochlorite. Any source of hypochlorite can be used toproduce a composition of the present invention as long as it provides asufficient amount of hypochlorite to achieve the purposes of the presentinvention. In a preferred embodiment, the compound used as the source ofhypochlorite provides at least 0.2 grams of hypochlorite per gram ofcompound (e.g., 0.23 moles hypochlorite per mole of compound). Incertain embodiments, the source of hypochlorite is tosylchloramide(N-chloro-tosylamide). In certain embodiments, the concentration of thesource of hypochlorite is in the range of from about 0.5% (w/v) to about3% (w/v). In certain embodiments, the concentration of the source ofhypochlorite in a composition of the present invention is in the rangeof from about 1% (w/v) to about 2.5% (w/v). In certain embodiments, theconcentration of the source of hypochlorite in a composition of thepresent invention is at least about 0.5% (w/v). In certain embodiments,the concentration of the source of hypochlorite in a composition of thepresent invention is at least about 1% (w/v). In certain embodiments,the concentration of the source of hypochlorite in a composition of thepresent invention is at least about 2% (w/v).

In certain embodiments, the concentration of the source of hypochloritein a composition of the present invention is in the range of from about0.5% (w/w) to about 3% (w/w). In certain embodiments, the concentrationof the source of hypochlorite in a composition of the present inventionis in the range of from about 0.5% (w/w) to about 1.5% (w/w). In certainembodiments, the concentration of the source of hypochlorite in acomposition of the present invention is in the range of from about 0.6%(w/w) to about 1.5% (w/w). In certain embodiments, the concentration ofthe source of hypochlorite in a composition of the present invention isat least about 0.5% (w/w). In certain embodiments, the concentration ofthe source of hypochlorite in a composition of the present invention isat least about 1% (w/w), at least about 1.1% (w/w), at least about 1.2%(w/w), at least about 1.3% (w/w), at least about 1.4% (w/w) or at leastabout 1.5% (w/w).

A therapeutic composition of the present invention further comprises anantimicrobial agent selected from biguanides, triguanides, bisbiguanidesand analogs thereof. Guanides, biguanides, biguanidines and triguanidesare unsaturated nitrogen containing molecules that readily obtain one ormore positive charges, which make them effective antimicrobial agents.The guanide, biguanide, biguanidine or triguanides, may provide bi-polarconfigurations of cationic and hydrophobic domains within a singlemolecule. Examples of guanides, biguanides, biguanidines and triguanidesthat are currently used as antibacterial agents include chlorhexidineand chlorohexidine salts, analogs and derivatives, such as chlorhexidineacetate, chlorhexidine gluconate and chlorhexidine hydrochloride,picloxydine, alexidine and polihexanide. Other examples of guanides,biguanides, biguanidines and triguanides that can be used incompositions of the present disclosure are chlorproguanil hydrochloride,proguanil hydrochloride, metformin hydrochloride, phenformin andbuformin hydrochloride. These bi-polar cationic antimicrobial agents mayalso be included and used in a polymeric form, such as, guanidepolymers, biguanide polymers, or polymers having side chains containingbiguanide moieties or other cationic functional groups, such asbenzalkonium groups or quarternium groups (e.g., quaternary aminegroups). In one or more embodiments, the cationic antimicrobial polymeris a polymeric biguanide compound. When applied to a substrate, such apolymer is known to form a barrier film that can engage and disrupt amicroorganism. An exemplary polymeric biguanide compound ispolyhexamethylene biguanide (PHMB) salts. Other exemplary biguanidepolymers include, but are not limited to, poly(hexamethylenebiguanide),poly(hexamethylenebiguanide) hydrochloride, poly(hexamethylenebiguanide)gluconate, poly(hexamethylenebiguanide) stearate, or a derivativethereof. In certain embodiments, a bisbiguanide selected fromchlorhexidine(N,N-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediamidine) and alexidine (N-(2-ethylhexyl)-1-3-(6-{N-[3-(2-ethylhexyl)carbamimidamidomethanimidoyl]amino}hexyl)carbamimid) is included andused in the compositions of the present disclosure. In certainembodiments, the source of chlorhexidine is selected from the groupconsisting of chlorhexidine gluconate, chlorhexidine acetate andchlorhexidine dihydrochloride. Chlorhexidine gluconate (4% w/v) iscommercially available, and is often provided in a solution combinedwith other ingredients such as poloxamer, isopropyl alcohol, lauramineoxide (surfactant), herbacol (fragrance), and colorant, such as FD&Cred) in water. Accordingly, a preparation of the subject invention canalso comprise these ingredients.

In certain embodiments, the concentration of a bisbiguanide in acomposition of the present invention is in the range of from about 1%(w/v) to about 10% (w/v). In certain embodiments, the concentration of abisbiguanide in a composition of the present invention is in the rangeof from about 1% (w/v) to about 6% (w/v). In certain embodiments, theconcentration of a bisbiguanide in a composition of the presentinvention is in the range of from about 1% (w/v) to about 4% (w/v). Incertain embodiments, the concentration of bisbiguanide in a compositionof the present invention is in the range of from about 1.2% (w/v) % toabout 2% (w/v). In certain embodiments, the concentration of abisbiguanide in a composition of the present invention is at least about1.2% (w/v). In certain embodiments, the concentration of a bisbiguanidein a composition of the present invention is at least about 1.8% (w/v).In certain embodiments, the concentration of a bisbiguanide in acomposition of the present invention is about 1.2% (w/v) or about 1.8%(w/v).

In certain embodiments, the concentration of a bisbiguanide in acomposition of the present invention is in the range of from about 0.5%(w/w) to about 5% (w/w). In certain embodiments, the concentration of abisbiguanide in a composition of the present invention is in the rangeof from about 0.5% (w/w) to about 3% (w/w). In certain embodiments, theconcentration of a bisbiguanide in a composition of the presentinvention is in the range of from about 0.5% (w/w) to about 1.5% (w/w).In certain embodiments, the concentration of a bisbiguanide in acomposition of the present invention is at least about 0.7% (w/w). Incertain embodiments, the concentration of a bisbiguanide in acomposition of the present invention is at least about 1.2% (w/w). Incertain embodiments, the concentration of a bisbiguanide in acomposition of the present invention is about 0.7% (w/w) or about 1.2%(w/w).

Therapeutic compositions of the present invention can optionallycomprise one or more compounds that produce oxygen. Any oxygen-producingcompound can be used to produce a composition of the present inventionas long as it is sufficiently stable and is able to produce a sufficientamount of oxygen to achieve the purpose of the present invention.Preferred oxygen-producing compounds are those that produce at least 60,at least 70, at least 80, at least 90 or at least 100 volumes of oxygenper volume of oxygen producing compound. For example, 1 cm³ of hydrogenperoxide will produce 100 cm³ of oxygen. In one embodiment the oxygenproducing compound is a peroxide. In certain embodiments, the source ofperoxide is selected from the group consisting of hydrogen peroxide,carbamide peroxide, benzoyl peroxide, urea peroxide, percarbamide orsodium percarbonate. In certain embodiments, the concentration of theoxygen-producing compound in a composition of the present invention isin the range of from about 0.01% (v/v) to about 0.1% (v/v). In certainembodiments, the concentration of the oxygen-producing compound in acomposition of the present invention is in the range of from about 0.03%(v/v) to about 0.09% (v/v). In certain embodiments, the concentration ofthe oxygen-producing compound in a composition of the present inventionis selected from about 0.03% (v/v), 0.06% (v/v) and 0.09% (v/v). Incertain embodiments, the concentration of the oxygen-producing compoundin a composition of the present invention is about 0.1% (v/v). Incertain embodiments, the concentration of the oxygen-producing compoundin a composition of the present invention is in the range of from about0.001% (v/v) to about 0.01% (v/v). In certain embodiments, theconcentration of the oxygen-producing compound in a composition of thepresent invention is in the range of from about 0.003% (v/v) to about0.009% (v/v). In certain embodiments, the concentration of theoxygen-producing compound in a composition of the present invention isselected from about 0.003% (v/v), 0.006% (v/v) and 0.009% (v/v). Incertain embodiments, the concentration of the oxygen-producing compoundin a composition of the present invention is about 0.01% (v/v).

Therapeutic compositions of the present invention can optionally includea poloxamer. Poloxamers are nonionic triblock copolymers composed of acentral hydrophobic chain of polypropylene oxide flanked by twohydrophilic chains of polyethylene oxide. Poloxamers are also known bythe trade name PLURONIC (BASF, Florham Park, N.J.). In certainembodiments, a therapeutic composition of the present inventioncomprises at least one of poloxamer 108, 185, 188, 237, 238, 338, 335,and/or 407. In certain embodiments, a therapeutic composition of thepresent invention comprises poloxamer 237. In certain embodiments, theconcentration of poloxamer in a composition of the present invention isin the range of from about 6% (w/v) to about 12% (w/v). In certainembodiments, the concentration of poloxamer in a therapeutic compositionof the present invention is at least about 6% (w/v). In certainembodiments, the concentration of poloxamer in a therapeutic compositionof the present invention is at least about 7% (w/v). In certainembodiments, the concentration of poloxamer in a therapeutic compositionof the present invention is at least about 7.5% (w/v), at least about 8%(w/v), at least about 9% (w/v), at least about 10% (w/v) or at leastabout 11% (w/v). In certain embodiments, the concentration of poloxamerin a therapeutic composition of the present invention is at least about11.5% (w/v).

In certain embodiments, the concentration of poloxamer in a compositionof the present invention is in the range of from about 4% (w/w) to about8% (w/w). In certain embodiments, the concentration of poloxamer in atherapeutic composition of the present invention is at least about 4%(w/w). In certain embodiments, the concentration of poloxamer in atherapeutic composition of the present invention is at least about 4.5%(w/w). In certain embodiments, the concentration of poloxamer in atherapeutic composition of the present invention is at least about 5%(w/w), at least about 5% (w/w), at least about 6% (w/w), at least about7% (w/w) or at least about 7.5% (w/w). In certain embodiments, theconcentration of poloxamer in a therapeutic composition of the presentinvention is at least about 11.5% (w/w).

In addition to the components discussed above, a therapeutic compositionof the present invention can optionally include a surfactant. Anysurfactant can be added to a therapeutic composition of the presentinvention as long as the resulting therapeutic composition issatisfactory for the purposes recited herein. For example, anionic,cationic, amphoteric and nonionic surfactants may be used in thecompositions of the present disclosure. In certain embodiments, thesurfactant is a non-ionic surfactant, which may include linear alcohol(C11) ethoxylate—POE-7, linear alcohol (C9-11) ethoxylate—POE-2.5,lauryl alcohol ethoxylate—POE-8, secondary alcohol ethoxylates,trideceth-2 carboxamide MEA, PEG-4 Rapeseed amide, PEG 5 Cocamide,cocamide DEA, lauramide MEA, cocamide MEA, lauramide DEA, oleamide DEA,caprylyl glucoside, myristyl glucoside, lauryl glucoside, myristylglucoside, caprylyl glucoside, decyl glucoside, N,N-dimethyldecanamide,sophorolipid, isopropyl myristate, sopropyl palmitate, glycereth-17cocoate, glycereth-6 cocoate, PEG/PPG-6/2 glyceryl cocoate, cetostearylalcohol, PEG 2 cocamine, PEG 2 tallow Amine, glycereth-7 caprylate,glycereth-7 caprate, caprylic triglyceride, capric triglyceride,glyceryl oleate, glyceryl stearate, lauryl lactyl lactate, polysorbate80 and combinations thereof. In certain embodiments, the surfactant isan amine oxide, which may include lauramine oxide, cocamidopropylamineoxide, lauryl/myristyl amidopropyl, amine oxide, tallow amine+2 eo,myristamine oxide, and combinations thereof. In specific embodiments,the surfactant is lauramine oxide (N,N-dimethyldodecylamine N-oxide). Incertain embodiments, the concentration of surfactant in a composition ofthe present invention is in the range of from about 0.1% (w/v) to about1% (w/v). In certain embodiments, the concentration of surfactant in acomposition of the present invention is in the range of from about 0.2%(w/v) to about 0.5% (w/v). In certain embodiments, the concentration ofsurfactant in a composition of the present invention is at least about0.2% (w/v). In certain embodiments, the concentration of surfactant in acomposition of the present invention is about 0.27% (w/v). In certainembodiments, the concentration of surfactant in a composition of thepresent invention is at least about 0.4% (w/v). In certain embodiments,the concentration of surfactant in a composition of the presentinvention is at about 0.42% (w/v).

In certain embodiments, the concentration of surfactant in a compositionof the present invention is in the range of from about 0.1% (w/w) toabout 0.5% (w/w). In certain embodiments, the concentration ofsurfactant in a composition of the present invention is in the range offrom about 0.1% (w/w) to about 0.3% (w/w). In certain embodiments, theconcentration of surfactant in a composition of the present invention isin the range of from about 0.15% (w/w) to about 0.27% (w/w). In certainembodiments, the concentration of surfactant in a composition of thepresent invention is at least about 0.15% (w/w). In certain embodiments,the concentration of surfactant in a composition of the presentinvention is at least about 0.27% (w/w).

In addition to the components discussed above, a therapeutic compositionof the present invention can optionally include a polyhydroxy acidselected from gactobionic acid, glucono delta-lactone (also known asgluconolactone), and blends thereof. In certain embodiments, theconcentration of the polyhydroxy acid in a composition of the presentinvention is in the range of from about 0.5% (w/v) to about 2% (w/v). Incertain embodiments, the concentration of the polyhydroxy acid in acomposition of the present invention is in the range of from about 0.5%(w/v) to about 1% (w/v). In certain embodiments, the concentration ofthe polyhydroxy acid in a composition of the present invention is in therange of from about 0.6% (w/v) to about 0.9% (w/v). In certainembodiments, the concentration of the polyhydroxy acid in a compositionof the present invention is at least about 0.5% (w/v). In certainembodiments, the concentration of the polyhydroxy acid in a compositionof the present invention is at least about 0.6% (w/v). In certainembodiments, the polyhydroxy acid of gluconolactone in a composition ofthe present invention is at least about 0.9% (w/v).

In certain embodiments, the concentration of the polyhydroxy acid in acomposition of the present invention is in the range of from about 0.2%(w/w) to about 0.8% (w/w). In certain embodiments, the concentration ofthe polyhydroxy acid in a composition of the present invention is in therange of from about 0.3% (w/w) to about 0.6% (w/w). In certainembodiments, the concentration of the polyhydroxy acid in a compositionof the present invention is in the range of from about 0.35% (w/w) toabout 0.6% (w/w). In certain embodiments, the concentration of thepolyhydroxy acid in a composition of the present invention is at leastabout 0.3% (w/w). In certain embodiments, the concentration of thepolyhydroxy acid in a composition of the present invention is at leastabout 0.35% (w/w). In certain embodiments, the concentration of thepolyhydroxy acid in a composition of the present invention is at leastabout 0.6% (w/w).

Liquid Formulation

As has been previously discussed, therapeutic compositions of thepresent invention can also be formulated as liquids. Such liquidformulations are useful for topical applications and as rinses. Liquidformulations of the present invention can, but need not, comprise all ofthe same ingredients as those disclosed for a paste formulation of thepresent invention, although in general, the concentrations of suchingredients are lower.

In certain embodiments, a liquid formulation of the present inventioncomprises a salt at a concentration sufficient to render the formulationhypertonic. In certain embodiments, the concentration of salt in aliquid formulation of the present invention is at least 200 mM. Incertain embodiments, a concentration of salt in a liquid formulation ofthe present invention is in the range of from about 0.3 molar to about0.8 molar. In certain embodiments, the concentration of salt in a liquidformulation of the present invention is in the range of from about 0.5molar to about 0.7 molar. In certain embodiments, the concentration ofsalt in a liquid formulation of the present invention is at least about0.5 molar. In on embodiment, the concentration of salt in a liquidformulation of the present invention is no greater than about 0.7 molar.In certain embodiments, the concentration of salt in a liquidformulation of the present invention is about 0.68 molar.

In certain embodiments, the concentration of salt in a liquidformulation of the present invention is in the range of about 3% (w/v)to about 4% (w/v). In certain embodiments, the concentration of salt ina liquid formulation of the present invention is at least about 3%(w/v). In certain embodiments, the concentration of salt in a liquidformulation of the present invention is no greater than about 4% (w/v).In certain embodiments, the concentration of salt in a liquidformulation of the present invention is about 3% (w/v). In certainembodiments, the concentration of the salt in a liquid formulation ofthe present invention is about 3.9% (w/v).

In certain embodiments, the concentration of salt in a liquidformulation of the present invention is in the range of from about 1.5%(w/w) to about 3% (w/w/). In certain embodiments, the concentration ofsalt in a liquid formulation of the present invention is in the range offrom about 1.8% (w/w) to about 2.5% (w/w). In certain embodiments, theconcentration of salt in a liquid formulation of the present inventionis a least about 1.9% (w/w). In certain embodiments, the concentrationof salt in a liquid formulation of the present invention is about 2%(w/w). In certain embodiments, the concentration of salt in a liquidformulation of the present invention is about 2.3% (w/w).

A liquid formulation of the present invention further comprises a sourceof bicarbonate. In certain embodiments, the source of the bicarbonate isa bicarbonate salt. In certain embodiments, the concentration ofbicarbonate salt in a liquid formulation of the present invention is inthe range of from about 0.8 molar to about 1.2 molar. In certainembodiments, the concentration of bicarbonate salt in a liquidformulation of the present invention is in the range of from about 0.8molar to about 1.1 molar. In certain embodiments, the concentration ofbicarbonate salt in a liquid formulation of the present invention is atleast 0.8 molar. In certain embodiments, the concentration ofbicarbonate salt in a liquid formulation of the present invention is atleast 1.1 molar. In certain embodiments, the concentration ofbicarbonate in a liquid formulation of the present invention is in therange of from about 0.5 molar to about 0.65 molar. In certainembodiments, the concentration of bicarbonate in a liquid formulation ofthe present invention is at least 0.5 molar.

In certain embodiments, the concentration of bicarbonate salt in aliquid formulation of the present invention is in the range of fromabout 7% (w/v) to about 9.5% (w/v). In certain embodiments, theconcentration of bicarbonate salt in a liquid formulation of the presentinvention is in the range of from about 7.3% (w/v) to about 9.4% (w/v).In certain embodiments, the concentration of bicarbonate salt in aliquid formulation of the present invention is at least 7.3% (w/v). Incertain embodiments, the concentration of bicarbonate salt in a liquidformulation of the present invention is at least 9.3% (w/v). In certainembodiments, the concentration of bicarbonate salt in a liquidformulation of the present invention is selected from about 7.3% (w/v)and about 9.3% (w/v).

In certain embodiments, the concentration of bicarbonate salt in aliquid formulation of the present invention is in the range of fromabout 4.5% (w/w) to about 6.0% (w/w). In certain embodiments, theconcentration of bicarbonate salt in a liquid formulation of the presentinvention is in the range of from about 4.5% (w/w) to about 5.5% (w/w).In certain embodiments, the concentration of bicarbonate salt in aliquid formulation of the present invention is at least 4.5% (w/w). Incertain embodiments, the concentration of bicarbonate salt in a liquidformulation of the present invention is at least 5.5% (w/w). In certainembodiments, the concentration of bicarbonate salt in a liquidformulation of the present invention is selected from about 4.6% (w/w)and about 5.5% (w/w).

In certain embodiments, the ratio of bicarbonate to salt in a liquidformulation of the present invention is in the range of from about 1:1.3to about 1:3. In certain embodiments, the ratio of bicarbonate to saltin a liquid formulation of the present invention is in the range of fromabout 1:1.3 to about 1:2.5. In certain embodiments, the ratio ofbicarbonate to salt in a liquid formulation of the present invention isabout 1:2.3. In certain embodiments, the ratio of bicarbonate to salt ina liquid formulation of the present invention is about 1:2.5.

A liquid formulation of the present invention further comprises a sourceof hypochlorite. In certain embodiments, the concentration of the sourceof hypochlorite in a liquid formulation of the present invention is inthe range of from about 0.05% (w/v) to about 0.3% (w/v). In certainembodiments, the concentration of the source of hypochlorite in a liquidformulation of the present invention is in the range of from about 0.1%(w/v) to about 0.25% (w/v). In certain embodiments, the concentration ofthe source of hypochlorite in a liquid formulation of the presentinvention is at least about 0.05% (w/v). In certain embodiments, theconcentration of the source of hypochlorite in a liquid formulation ofthe present invention is at least about 0.1% (w/v). In certainembodiments, the concentration of the source of hypochlorite in a liquidformulation of the present invention is at least about 0.2% (w/v).

In certain embodiments, the concentration of the source of hypochloritein a liquid formulation of the present invention is in the range of fromabout 0.05% (w/w) to about 0.3% (w/w). In certain embodiments, theconcentration of the source of hypochlorite in a liquid formulation ofthe present invention is in the range of from about 0.05% (w/w) to about0.15% (w/w). In certain embodiments, the concentration of the source ofhypochlorite in a liquid formulation of the present invention is in therange of from about 0.06% (w/w) to about 0.15% (w/w). In certainembodiments, the concentration of the source of hypochlorite in a liquidformulation of the present invention is at least about 0.05% (w/w). Incertain embodiments, the concentration of the source of hypochlorite ina liquid formulation of the present invention is at least about 0.1%(w/w), at least about 0.11% (w/w), at least about 0.12% (w/w), at leastabout 0.13% (w/w), at least about 0.14% (w/w) or at least about 0.15%(w/w).

A liquid formulation of the present invention further comprises abisbiguanide. In certain embodiments, the concentration of bisbiguanidein a liquid formulation of the present invention is in the range of fromabout 0.1% (w/v) to about 1% (w/v). In certain embodiments, theconcentration of bisbiguanide in a liquid formulation of the presentinvention is in the range of from about 0.1% (w/v) to about 0.6% (w/v).In certain embodiments, the concentration of bisbiguanide in a liquidformulation of the present invention is in the range of from about 0.1%(w/v) to about 0.4% (w/v). In certain embodiments, the concentration ofbisbiguanide in a liquid formulation of the present invention is in therange of from about 0.12% (w/v) to about 0.2% (w/v). In certainembodiments, the concentration of bisbiguanide in a liquid formulationof the present invention is at least about 0.12% (w/v). In certainembodiments, the concentration of bisbiguanide in a liquid formulationof the present invention is at least about 0.18% (w/v). In certainembodiments, the concentration of bisbiguanide in a liquid formulationof the present invention is about 0.12% (w/v) or about 0.18% (w/v).

In certain embodiments, the concentration of bisbiguanide in a liquidformulation of the present invention is in the range of from about 0.05%(w/w) to about 0.5% (w/w). In certain embodiments, the concentration ofbisbiguanide in a liquid formulation of the present invention is in therange of from about 0.05% (w/w) to about 0.3% (w/w). In certainembodiments, the concentration of bisbiguanide in a liquid formulationof the present invention is in the range of from about 0.05% (w/w) toabout 0.15% (w/w). In certain embodiments, the concentration ofbisbiguanide in a liquid formulation of the present invention is atleast about 0.07% (w/w). In certain embodiments, the concentration ofbisbiguanide in a liquid formulation of the present invention is atleast about 0.12% (w/w). In certain embodiments, the concentration ofbisbiguanide in a liquid formulation of the present invention is about0.07% (w/w) or about 0.12% (w/w).

A liquid formulation of the present invention can optionally include acompound that produces oxygen. In one embodiment the oxygen producingcompound is peroxide. In certain embodiments, the concentration of theoxygen-producing compound in a liquid formulation of the presentinvention is in the range of from about 0.001% (v/v) to about 0.01%(v/v). In certain embodiments, the concentration of oxygen-producingcompound in a liquid formulation of the present invention is in therange of from about 0.003% (v/v) to about 0.009% (v/v). In certainembodiments, the concentration of oxygen-producing compound in a liquidformulation of the present invention is selected from about 0.003%(v/v), 0.006% (v/v) and 0.009% (v/v). In certain embodiments, theconcentration of oxygen-producing compound in a liquid formulation ofthe present invention is about 0.01% (v/v).

Liquid formulations of the present invention can optionally include apoloxamer. In certain embodiments, the concentration of poloxamer in aliquid formulation of the present invention is in the range of fromabout 0.6% (w/v) to about 1.2% (w/v). In certain embodiments, theconcentration of poloxamer in a liquid formulation of the presentinvention is at least about 0.6% (w/v). In certain embodiments, theconcentration of poloxamer in a liquid formulation of the presentinvention is at least about 0.7% (w/v). In certain embodiments, theconcentration of poloxamer in a liquid formulation of the presentinvention is at least about 0.75% (w/v), at least about 0.8% (w/v), atleast about 0.9% (w/v), at least about 1.0% (w/v) or at least about 1.1%(w/v). In certain embodiments, the concentration of poloxamer in aliquid formulation of the present invention is at least about 1.2%(w/v).

In certain embodiments, the concentration of poloxamer in a liquidformulation of the present invention is in the range of from about 0.4%(w/w) to about 0.8% (w/w). In certain embodiments, the concentration ofpoloxamer in a liquid formulation of the present invention is at leastabout 0.4% (w/w). In certain embodiments, the concentration of poloxamerin a liquid formulation of the present invention is at least about 0.45%(w/w). In certain embodiments, the concentration of poloxamer in aliquid formulation of the present invention is at least about 0.5%(w/w), at least about 0.6% (w/w), at least about 0.7% (w/w) or at leastabout 0.75% (w/w). In certain embodiments, the concentration ofpoloxamer in a liquid formulation of the present invention is at leastabout 1.2% (w/w).

In addition to the components discussed above, a liquid formulation ofthe present invention can optionally include a surfactant. In certainembodiments, the concentration of surfactant in a liquid formulation ofthe present invention is in the range of from about 0.01% (w/v) to about0.1% (w/v). In certain embodiments, the concentration of surfactant in aliquid formulation of the present invention is in the range of fromabout 0.02% (w/v) to about 0.05% (w/v). In certain embodiments, theconcentration of surfactant in a liquid formulation of the presentinvention is at least about 0.02% (w/v). In certain embodiments, theconcentration of surfactant in a liquid formulation of the presentinvention is about 0.027% (w/v). In certain embodiments, theconcentration of surfactant in a liquid formulation of the presentinvention is at least about 0.04% (w/v).

In certain embodiments, the concentration of surfactant in a liquidformulation of the present invention is in the range of from about 0.01%(w/w) to about 0.05% (w/w). In certain embodiments, the concentration ofsurfactant in a liquid formulation of the present invention is in therange of from about 0.01% (w/w) to about 0.03% (w/w). In certainembodiments, the concentration of surfactant in a liquid formulation ofthe present invention is in the range of from about 0.015% (w/w) toabout 0.027% (w/w). In certain embodiments, the concentration ofsurfactant in a liquid formulation of the present invention is at leastabout 0.015% (w/w). In certain embodiments, the concentration ofsurfactant in a liquid formulation of the present invention is at leastabout 0.027% (w/w).

In addition to the components discussed above, a liquid formulation ofthe present invention can optionally include a polyhydroxy acid selectedfrom gactobionic acid, glucono delta-lactone (also known asgluconolactone), and blends thereof. In certain embodiments, theconcentration of a polyhydroxy acid in a liquid formulation of thepresent invention is in the range of from about 0.05% (w/v) to about0.2% (w/v). In certain embodiments, the concentration of a polyhydroxyacid in a liquid formulation of the present invention is in the range offrom about 0.05% (w/v) to about 0.1% (w/v). In certain embodiments, theconcentration of a polyhydroxy acid in a liquid formulation of thepresent invention is in the range of from about 0.06% (w/v) to about0.09% (w/v). In certain embodiments, the concentration of a polyhydroxyacid in a liquid a formulation of the present invention is at leastabout 0.05% (w/v). In certain embodiments, the concentration of apolyhydroxy acid in a liquid formulation of the present invention is atleast about 0.06% (w/v). In certain embodiments, the concentration of apolyhydroxy acid in a liquid formulation of the present invention is atleast about 0.09% (w/v).

In certain embodiments, the concentration of a polyhydroxy acid in aliquid formulation of the present invention is in the range of fromabout 0.02% (w/w) to about 0.08% (w/w). In certain embodiments, theconcentration of a polyhydroxy acid in a liquid formulation of thepresent invention is in the range of from about 0.03% (w/w) to about0.06% (w/w). In certain embodiments, the concentration of a polyhydroxyacid in a liquid formulation of the present invention is in the range offrom about 0.035% (w/w) to about 0.06% (w/w). In certain embodiments,the concentration of a polyhydroxy acid in a liquid formulation of thepresent invention is at least about 0.03% (w/w). In certain embodiments,the concentration of a polyhydroxy acid in a liquid formulation of thepresent invention is at least about 0.035% (w/w). In certainembodiments, the concentration of a polyhydroxy acid in a liquidformulation of the present invention is at least about 0.06% (w/w).

Compositions and formulations of the present invention have an alkalinepH. Without intending to being bound by theory, it is believed thatalkaline formulations of the present invention prevent the formation ofperoxynitrite (superoxide nitrite) from super oxide and nitric oxide. Itis further believed that an alkaline formulation of the presentinvention neutralizes the acidic environment produced by proton releaseduring injury. The net results of these effects is inhibition ofinflammatory pathways and a switch from a catabolic state to an anabolicstate. Thus, in certain embodiments, the pH of a liquid formulation ofthe present invention is greater than 7. In certain embodiments, the pHof a liquid formulation of the present invention is in the range of fromabout 7 to about 9.5. In certain embodiments, the pH of a liquidformulation of the present invention is selected from the groupconsisting of about 7.2, about 7.4, about 7.6 about 7.8, about 8.0,about 8.2, about 8.4, about 8.6, about 8.8, about 9.0, about 9.2 andabout 9.4.

In addition to the components discussed above, compositions of thepresent invention can optionally include a compound selected from thegroup consisting of an anti-bacterial compound, an anti-viral compound,an anti-fungal compound and an anti-cancer compound. Examples ofanti-bacterial agents include, but are not limited to alcohol, analides(e.g., triclocarban), bisphenols (e.g., triclosan), quarternary ammoniumcompounds (e.g., benzalkonium chloride) and antibiotics. Examples ofanti-viral agents include, but are not limited to, acyclovir andfamciclovir. Examples of anti-fungal agents include, but are not limitedto, amphotericin B, clotrimazole, fluconazole, abafungin, amorolfin andcaspofungin. Examples of anti-cancer agents include, but are not limitedto, 5-fluorouracil, hydroxyurea, cisplatin and vinblastine.

While not intending to be limited by theory, it is contemplated that thecomposition, and its individual ingredients function together,symbiotically and synergistically, as described in the following table:

INGREDIENT PROPOSED EFFECT SALT(S) changes osmolarity from hypotonic tohypertonic solution BICARBONATE OF changes pH to alkaline andneutralizes acidity; direct microbial SODA activity; neutralizes toxins,reduces reactions to other chemicals in compositions; promotes healing;neutralizes protonic release due to inflammatory cascade; may preventformation of superoxide nitrite and thereby reduce inflammatory cascadeand thus interfere with pain pathways PEROXIDE oxygen changesenvironment from anaerobic to aerobic, may stimulate healing SURFACTANTlyses bacterial cell walls and so destroys bacteria CHLORAMINE T strongantimicrobial effect on bacterial/viral/fungal cell walls and DNA, sodestroying the bacteria/virus/fungus while preventing formation of drugsensitivity or resistance CHLORHEXIDINE strong antimicrobial effects onbacteria, viruses and fungus GLUCONATE

The compositions disclosed herein may be formulated in the form of apaste, a gel, a liquid (e.g. for topical or injectable administration),a putty, a foam, an ointment, a cream, a toothpaste, or in the form ofan oral care composition.

Formulations for the topical or transdermal administration ofcompositions of this disclosure include powders, sprays, ointments,pastes, creams, lotions, gels, solutions, patches, drops and inhalants.The compositions may be mixed under sterile conditions with apharmaceutically-acceptable carrier, and with any buffers, orpropellants which may be required.

The ointments, pastes, creams and gels may contain, in addition to thecomposition ingredients described above, excipients, such as animal andvegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulosederivatives, polyethylene glycols, silicones, bentonites, silicic acid,talc and zinc oxide, or mixtures thereof.

Powders and sprays can contain, in addition to the compositioningredients described above, excipients such as lactose, talc, silicicacid, aluminum hydroxide, calcium silicates and polyamide powder ormixtures of these substances.

Sprays can additionally contain customary propellants such aschlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, suchas butane and propane.

Drops, such as nose drops, may be formulated with an aqueous ornonaqueous base also comprising one or more dispersing agents,solubilizing agents or suspending agents. Liquid sprays are convenientlydelivered from pressurized packs. Drops can be delivered by means of asimple dropper-capped bottle or by means of a plastic bottle adapted todeliver liquid contents drop-wise by means of a specially shapedclosure.

Liquid dosage forms for administration of the compositions of thisdisclosure include pharmaceutically-acceptable emulsions,microemulsions, solutions, suspensions, syrups and elixirs. In additionto the active ingredient, the liquid dosage forms may contain inertdiluents commonly used in the art, such as, water or other solvents,solubilizing agents and emulsifiers, such as ethyl alcohol, isopropylalcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzylbenzoate, propylene glycol, 1,3-butylene glycol, oils (in particular,cottonseed, groundnut, corn, germ, olive, castor and sesame oils),glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acidesters of sorbitan, and mixtures thereof.

By “oral care composition” is meant a product, which in the ordinarycourse of usage, is not intentionally swallowed for purposes of systemicadministration of particular therapeutic agents, but is rather retainedin the oral cavity for a time sufficient to contact substantially all ofthe dental surfaces and/or oral tissues for purposes of oral activity.The oral care composition may be in various forms including toothpaste,dentifrice, tooth gel, subgingival gel, mouth rinse, solutions, mousse,foam, denture care product, mouth spray, lozenge or chewable tablet.These oral care compositions of this disclosure may also be incorporatedonto floss, strips or films for direct application or attachment to oralsurfaces or integrated into a device or applicator such as a toothbrushor roll-ons. Such applicators may be for single or multiple use.

Preferred paste formulations are sufficiently viscous to remain in placefollowing topical application and elute active ingredients over time.Such viscous formulations may thereby be applied adjacent to an areasurrounding a wound, abrasion, infection or the like.

However, other formulations can also be used. As non-limiting examples,the subject compositions can be formulated into a powder, a dentifrice,a lozenge, a buccal adhesive patch, an oral spray, coatings that adhereto the oral cavity, chewing gum and the like. Such compositions can beformulated as is known to those of skill in the art to achieve thedesired therapeutic effect(s) following topical application to skin, anopen or closed wound, a mucus membrane, any portion of the oral cavity,and the like.

In some embodiments, the formulations of compositions of this disclosureinclude thickening or gelling agents such aspolyoxyethylene/polyoxy-propylene block copolymers or carbomer polymers.

A composition utilizing carbamide peroxide, rather than hydrogenperoxide, was prepared by mixing together carbamide peroxide with theingredients of the therapeutic compositions of this disclosure. Suchformulations using the solid carbamide peroxide can be formulated as athick gel.

In some embodiments, the formulations or compositions of this disclosurecomprise a polymeric material (or polymeric precursor which forms apolymer, gel, hydrogel, or viscous fluid in situ). Exemplary polymersinclude polylactic acid, polyglycolic acid, poly(L-lactide) (PLLA),poly(D,L-lactide) (PLA) polyglycolic acid [polyglycolide (PGA)],poly(L-lactide-co-D,L-lactide) (PLLA/PLA), poly(L-lactide-coglycolide)(PLLA/PGA), poly(D, L-lactide-co-glycolide) (PLA/PGA),poly(glycolide-cotrimethylene carbonate) (PGA/PTMC),poly(D,L-lactide-co-caprolactone) (PLA/PCL),poly(glycolide-co-caprolactone) (PGA/PCL), poly(oxa)esters, polyethyleneoxide (PEO), polydioxanone (PDS), polypropylene fumarate, poly(ethylglutamate-co-glutamic acid), poly(tert-butyloxy-carbonylmethylglutamate), polycaprolactone (PCL), polycaprolactone cobutylacrylate,polyhydroxybutyrate (PHBT), polyhydroxybutyrate, poly(phosphazene),polyphosphate ester), poly(amino acid), polydepsipeptides,polyiminocarbonates, poly[(97.5% dimethyl-trimethylenecarbonate)-co-(2.5% trimethylene carbonate)], poly(orthoesters),polycarbonates, polyiminocarbonates, polyphosphonates, polyethyleneoxide, polyalkylene oxides, and hydroxypropylmethylcellulose.

In some embodiments, the formulations include a binder, for examplepolyethylene glycol (PEG). In particular embodiments, the PEG is PEG400. The formulations disclosed herein may contain ingredients typicallyincorporated into oral health care compositions. Suitable ingredientscan include, without limitation, abrasive polishing materials, sudsingagents, flavoring agents, humectants, binders, water and sweeteningagents, in particular, high intensity sweeteners, such as sucralose,aspartame and saccharin. Abrasives which may be used in the compositionsdisclosed herein include alumina and hydrates thereof, such as alphaalumina trihydrate, magnesium trisilicate, magnesium carbonate,aluminosilicate, such as calcined aluminum silicate and aluminumsilicate, calcium carbonate, zirconium silicate, powdered polyethylene,silica xerogels, hydrogels and aerogels and the like. Also suitable asabrasive agents are calcium pyrophosphate, insoluble sodiummetaphosphate, calcium carbonate, dicalcium orthophosphate, particulatehydroxyapatite and the like.

Dyes/colorants suitable for compositions of this disclosure, such as FD& C Blue #1, FD & C Yellow #10, FD & C Red #40, and the like, may beemployed in the subject formulations as well. Various other optionalingredients may also be included in the disclosed compositions,including without limitation, as preservatives, vitamins (such asvitamins C and E), anti-plaque agents such as stannous salts, coppersalts, strontium salts and magnesium salts, pH adjusting agents,anti-caries agents such as calcium glycerophosphate, sodiumtrimetaphosphate; and anti-staining compounds such as silicone polymers,plant extracts and mixtures thereof. Additionally, polymers,particularly anionic polymers, such as polycarboxylates orpolysulfonates, or polymers containing both a carboxylate and asulfonate moiety, phosphonate polymers or polyphosphates may beincluded. Other optional carrier components fulfill multiple functions,for example, acting both as carriers and flavorants. Nonlimitingrepresentative flavor oils include spearmint oil, cinnamon oil, oil ofwintergreen (methyl salicylate), peppermint oil, clove oil, bay oil,anise oil, eucalyptus oil, thyme oil, cedar leaf oil, oil of nutmeg,allspice, oil of sage, mace, oil of bitter almonds, and cassia oil.Menthol, peppermint oil and eugenol are examples of carriers as well asbeing organic flavorants that may be used separately or in combinationsin the formulation of the compositions of this disclosure.

When formulated as mouthwashes, oral rinses, throat gargles, or similarpreparations, such preparations can include water/alcohol solutions,flavor components, humectants, sweeteners, sudsing agents, andcolorants. These liquid formulations may include ethanol, at a level offrom 0 to 60%, preferably from 5 to 30%, by weight.

In certain embodiments, the compositions of this disclosure may beformulated within an implantable material, such as a three-dimensionalbody defining one or more reservoirs for receiving the composition(s).Such implantable materials are preferably wettable with biologicalfluids. In some embodiments, the wettable materials may also bedisrupted or dissolve in contact with a biological fluid.

In a further embodiment, medical devices or implants may be coated withthe compositions of this disclosure. Thus, coated medical devices orimplants are provided as embodiments of the invention. Such devices orimplants include catheters, surgical pins, pacemaker capsules, stents,shunts, endotracheal or gastrointestinal tubes, surgical or dentalimplants, sutures, electrodes, dialysis devices and bandages coated withor impregnated with compositions of this disclosure.

Compositions of the present disclosure may also be introduced into acollagen plug that may be adapted to elute the composition into anopening or body cavity. In this manner, the composition may be elutedinto, for example, a wound from the collagen plug. Thus, one embodimentof the invention is a collagen plug infused with a composition of thisdisclosure.

The compositions of this disclosure are useful in a wide variety ofmethods in which soft tissues and/or bone is/are altered. The methodsencompass any type of tissue modifications, including tissue repair,regeneration, reconstruction and remodeling. Compositions andformulations of the present invention can also be used in tissue orimplant-guided regeneration. Without being bound by theory, it isbelieved that the compositions and formulations aid in such repair andregeneration by inhibiting or killing infectious organisms and byreducing inflammation and pain at the site of injury or repair. Theseprocesses can encompass any type of tissue modification, includingwholly internal processes as well as processes that include or affectthe skin or an orifice such as the mouth or nose (e.g., the compositionsdescribed herein can be used in dental procedures). Thus, in addition totheir use in conjunction with tissue fixation devices or synthetic bonesubstitutes or prostheses, the compositions of this disclosure may alsobe used in conjunction with the use of devices for attachment oforthopedic hardware (e.g., as screws for bone plates or screws totemporary secure hip stems) or in the context of reconstructive orcosmetic surgery, or repair bone, chondral and/or osteochondral defects,as often used in sports medicine implants.

In one embodiment, a composition or formulation of the present inventionis used as an antiseptic mouth rinse or throat gargle. Such a rinse orgargle can be used, for example, to treat a sore throat (pharyngitis),to kill organisms that cause illness such as cold and flu, to killorganisms that cause bad breath, gingivitis, plaque, to kill organismsthat cause mouth sores (e.g., herpes), to treat fungal infections of themouth and to treat canker sores and other ulcerations of the mouth. Sucha rinse or gargle can also be used to reduce inflammation in the mouth,promote growth of mouth tissue, reduce or eliminate pain in the mouthand to treat cancer and/or cancerous lesions of the mouth. Oneembodiment is a composition of the present invention when used as anantiseptic oral rinse or a throat gargle. One embodiment of the presentinvention is the use of a composition of the present invention in thepreparation of a medicament for oral disinfection. One embodiment of thepresent invention is the use of a composition of the present inventionin the preparation of a medicament for use as a throat gargle.

In certain embodiments, a composition or formulation of the presentinvention is used as an antiseptic rinse for sinuses. Such rinsing ofthe sinuses provides multiple benefits, such as; relieving nasalcongestion (e.g., chronic rhinitis) and sinusitis due to infection withorganisms that cause illness, such as, cold or flu; relieving sorethroat pain; relieving post-nasal drip; relieving symptoms to dueallergies due to mold, mildew and/or fungi; and relieving symptoms dueto airborne allergens, such as, pollen, pet dandruff, dust mites, andthe like. A sinus rinse can also be used for reducing generalinflammation of the sinuses as well as reducing or eliminating sinuspain. One embodiment is a composition of the present invention when usedas an antiseptic sinus rinse. One embodiment of the present invention isthe use of a composition of the present invention in the preparation ofa medicament for rinsing the sinuses. One embodiment of the presentinvention is the use of a composition of the present invention in thepreparation of a medicament for disinfection of the sinuses.

In certain embodiments, compositions and formulations of the presentinvention can be used in dental procedures. In one embodiment, aformulation of the present invention is used as an anti-bacterial mouthrinse. Such a rinse can be used to treat infections of the mouth,promote angiogenesis in oral tissue, promote growth of new tissue in themouth, reduce or eliminate mouth pain or reduce inflammation in themouth. In one embodiment, a composition or formulation of the presentinvention is used to treat inflamed or damaged tissue resulting from atooth extraction. In one embodiment, a composition or formulation of thepresent invention is used to treat inflamed or damaged tissue resultingfrom oral surgery. In addition to treating infections and reducinginflammation, such compositions and formulations can also be used tohelp promote angiogenesis and tissue regeneration following trauma inthe mouth, tooth extractions or oral surgery. In this regard, it shouldbe appreciated that compositions and formulations of the presentinvention can be applied directly to the tissue being treated or theycan be applied in the form of plugs (e.g., collagen plugs) or allografts(e.g., tissue grafts, bone grafts), that have been impregnated with acomposition or formulation of the present invention. One embodiment is acomposition of the present invention when used as part of a dentalprocedure. One embodiment of the present invention is the use of acomposition of the present invention in the preparation of a medicamentfor use in a dental procedure.

In addition to the dental applications discussed above, the inventorshave discovered that compositions and formulations of the presentinvention provide the surprising and unexpected benefit of reducing painfrom dental procedures. Such procedures include, but are not limited to,treating periodontal disease (e.g., operculitis), periodontal scaling,root planning, curettage, tooth extractions, oral surgery, root canals,crown placements, bridge placements, and the like. In addition to theuses described above, the inventors have discovered that irrigation ofan inflamed periodontal sulcus (“pocket”), resulted in shrinkage of thepocket by as much as 3-5 millimeters. Thus, in one embodiment, acomposition or formulation of the present invention can be used toirrigate a periodontal sulcus. Moreover, the inventors have furtherdiscovered that, surprisingly, compositions and formulations of thepresent invention can be used to reduce numbness of the mouth andsurrounding tissue resulting from anesthesia, without reducing theanalgesic effect of the anesthesia. One embodiment is a composition ofthe present invention when used to reduce 1) pain or 2) numbnessresulting from anesthesia. One embodiment of the present invention isthe use of a composition of the present invention in the preparation ofa medicament for treating pain or reducing numbness resulting fromanesthesia.

While the above discussion discloses dental uses of compositions andformulations of the present invention, such compositions andformulations can also be used in surgical procedures unrelated to dentalprocedures. Thus, in certain embodiments, compositions and formulationsof the present invention can be used in surgical procedures. In oneembodiment, a composition or formulation of the present invention can beused as a general disinfectant prior to, during or after surgery. Forexample, a composition or formulation of the present invention can beused to disinfect hands or as a skin scrub prior to surgery. In certainembodiments, a composition or formulation of the present invention canbe used to decontaminant or disinfect a surgical wound during orfollowing surgery. For example, a paste or liquid formulation of thepresent invention can be used to scrub a surgical site prior to surgery.As a further example, a liquid composition of the present invention canbe used to irrigate a wound or incision during surgery.

In certain embodiments, a composition or formulation of the presentinvention is used during surgery to reduce inflammation. In certainembodiments, a composition or formulation of the present invention isused during surgery to promote angiogenesis and/or the growth of newtissue.

In addition, the inventors have discovered that treatment of woundsusing a composition or formulation of the present invention reduces oreliminates scar formation following regeneration of the wound tissue.Thus, in one embodiment, a composition or formulation of the presentinvention is used to reduce scar formation in a wound. Such a wound canbe, for example, a surgical incision or a wound resulting from trauma,such as bullet wound, knife wound or a compound fracture. One embodimentis a composition of the present invention when used in a surgicalprocedure. One embodiment of the present invention is the use of acomposition of the present invention in the preparation of a medicamentfor use in a surgical procedure.

In addition to the treatment of tissue prior to, during or aftersurgery, compositions and formulations of the present invention can beused to reduce pain prior to, during or following surgery. In thisregard, a composition or formulation of the present invention can beadministered prior to, during or following surgery.

In addition to wounds resulting from dental or surgical procedures, incertain embodiments, a composition or formulation of the presentinvention can be used to treat any wound. While not intending to bebound by theory, it is believed that compositions and formulations ofthe present invention promote wound healing by reducing or eliminatinginfectious organisms and promoting capillary bed formation andangiogenesis. Wounds that can be treated with compositions orformulations of the present invention include open wounds, wounds thatare in the process of healing (e.g., closing) or wounds that arerecently healed (e.g., closed). Such wounds can be due to any injurythat results in a wound. Such wounds include, for example, cancer sores,lesions of the throat and mouth, scrapes, abrasions, evulsions,ulcerations (including diabetic ulcerations), penetrating wounds, bitewounds (human and animal), incisions, stab wounds, bullet wounds, warwounds, wounds resulting from shrapnel, wounds due to thermal burns andwounds resulting from chemical burns. In one embodiment, a compositionor formulation of the present invention is used to treat an infection ina wound. Such treatment can be to prevent an infection or to reduce oreliminate an active infection. The infectious organism may or may not beresistant to antibiotics or other common compounds used to treatinfections. In one embodiment, a composition or formulation of thepresent invention is used to reduce or eliminate scarring from a wound.In one embodiment, a composition or formulation of the present inventionis used to debride a wound. In one embodiment, a composition orformulation of the present invention is used to promote angiogenesis orgrowth of new tissue. In one embodiment, a composition or formulation ofthe present invention is used to reduce inflammation in a wound. In oneembodiment, a composition or formulation of the present invention isused to reduce or eliminate pain in a wound. One embodiment is acomposition of the present invention when used to treat a wound. Oneembodiment of the present invention is the use of a composition of thepresent invention in the preparation of a medicament for treating awound.

Compositions and formulations of the present invention can also be usedto treat dermatological conditions. In one embodiment, a composition orformulation of the present invention is included in a facial wash. Inone embodiment, a composition or formulation of the present invention isused to treat a skin infection (e.g., staph infection, chicken pox,herpes zoster virus, etc.). In one embodiment, a composition orformulation of the present invention is used to treat acne. In oneembodiment, a composition or formulation of the present invention isused to treat rosacea. In one embodiment, a composition or formulationof the present invention is used to treat inflammation of the skin. Inone embodiment, a composition or formulation of the present invention isused to treat a skin lesion (e.g., lump, bump, swelling, wheal, flare)resulting from an insect bite or sting. In one embodiment, a compositionor formulation of the present invention is used to treat a skin lesion(e.g., lump, bump, swelling, wheal, flare) resulting from an allergicreaction (e.g., contact dermatitis). One embodiment is a composition ofthe present invention when used to treat a dermatological condition. Oneembodiment of the present invention is the use of a composition of thepresent invention in the preparation of a medicament for treating adermatological condition.

In addition to the uses described above, the inventors have discoveredthat compositions and formulations of the present invention can be usedto treat lesions resulting from, or otherwise relating to, tumors. Suchlesions can be pre-cancerous lesions, or they can be lesions that resultfrom direct damage by tumor cells, or damage resulting from an immuneresponse to the growth of tumor cells. Such lesions may also be due totissue damage resulting from treatment of a tumor with an anti-tumoragent such as a chemotherapeutic agent. In one embodiment, a compositionof the present invention is used to treat a pre-cancerous lesion. In oneembodiment, a composition of the present invention is used to treat acancerous lesion. In one embodiment, a composition of the presentinvention is used to treat a tumor or cancer-related lesion. In oneembodiment, a composition of the present invention is used to reduceinflammation resulting from a cancer or a tumor. In one embodiment, acomposition of the present invention is used to reduce pain resultingfrom a cancer or a tumor. One embodiment is a composition of the presentinvention when used to treat a lesion related to cancer or a tumor. Oneembodiment of the present invention is the use of a composition of thepresent invention in the preparation of a medicament for treating alesion related to cancer or a tumor.

In certain embodiments, a composition or formulation of the presentinvention is used to treat a cancer or tumor. Such cancers or tumors canbe benign or malignant. Such cancers or tumors can be systemic orlocalized. In a preferred embodiment, the tumor or cancer being treatedis localized. Compositions and formulations of the present invention canbe used to treat ay tumor although preferred tumors are those to which acomposition or formulation of the present invention can be applieddirectly. In one embodiment, a composition or formulation of the presentinvention is used to inhibit the growth of tumor cells. In oneembodiment, a composition or formulation of the present invention isused to kill tumor cells. One embodiment is a composition of the presentinvention when used to treat a cancer or a tumor. One embodiment of thepresent invention is the use of a composition of the present inventionin the preparation of a medicament for treating a cancer or a tumor.

In one embodiment, a composition or formulation of the present inventionis used to prepare a biomaterial scaffold product. Biomaterial‘scaffold’ products of various materials, shapes and sizes are wellknown for use in a variety of medical applications such as wound closuresystems, including vascular wound repair devices, hemostatic dressings,patches and glues, sutures, drug delivery and in tissue engineeringapplications, such as, for example, scaffolding, ligament prostheticdevices and in products for long-term or bio-degradable implantationinto the human body. The scaffold serves as both a physical support andan adhesive substrate during implantation. The ideal bioabsorbablescaffold has sufficient mechanical properties to perform its primaryfunction but over time the implant should ideally get replaced bynatural tissue that is surrounding the implant. In certain embodimentsthe material releases compounds that aid the repair and replacementprocess. Tissue engineered scaffolds for use in such applications arewell known and may include, for example, woven or non-woven networks ofbiocompatible fibers, biocompatible and restorable polymers or spongesor microspheres, synthetic or recovered bone fragments, hydrogels,foams, silks, and the like.

Thus, certain embodiments of the invention include such biomaterialscontaining therapeutic compositions of the present disclosure. To formthese materials, the biomaterial is mixed with a therapeutic agent priorto forming the material or loaded into, or onto, the material after itis formed (i.e., the biomaterial is impregnated, soaked in or coatedwith, a composition of this disclosure after formation). The therapeuticcompositions, as applied to or present in these biomaterials may bepresent as a liquid, a finely divided solid, a paste, or any otherappropriate physical form that is compatible with and does not adverselyaffect the performance of the biomaterial.

The biomaterial-therapeutic composition combinations of this embodimentmay be prepared for storage under conditions suitable for thepreservation of activity of the composition as well as maintaining theintegrity of the biomaterial, and are typically suitable for storage atambient or refrigerated temperatures.

Compositions and formulations of the present invention can beadministered directly to a wound area, topically as a rinse, drench, orointment, or by subcutaneous or intra-lesional injection. Similarly,these compositions can be incorporated onto or into wound dressingmaterials such as a bandage, patch, collagen plug, or suture material.

When employed as pharmaceuticals, the compositions of the presentdisclosure are administered in the form of pharmaceutical formulations.These formulations can be administered by a variety of routes includingoral, rectal, topical, subcutaneous, intramuscular, and intranasal.Preferably, these formulations are administered topically when used totreat wounds or infections. Such formulations are prepared in a mannerwell known in the pharmaceutical art and comprise at least onecomposition of the present disclosure.

Thus, other aspects of the invention include methods of using of acomposition of this disclosure in the preparation of a medicament forthe treatment of a mammal in need of such treatment suffering a diseaseor disorder as described above. This aspect of the invention includescompositions of this disclosure for use in the treatment of a mammal inneed of such treatment suffering a disease or disorder as describedabove. In certain embodiments, methods of treatment according to thisinvention include treatment of a mammal in need of such treatmentsuffering a disease or disorder as described above comprisingadministering an effective amount of a composition of this disclosure toan individual in need thereof.

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how tomake and use the embodiments, and are not intended to limit the scope ofwhat the inventors regard as their invention nor are they intended torepresent that the experiments below are all or the only experimentsperformed. Efforts have been made to ensure accuracy with respect tonumbers used (e.g. amounts, concentrations, times, etc.) but someexperimental errors and deviations should be accounted for. Standardmedical and scientific abbreviations are used.

Example 1

This Example illustrates the preparation of a paste of the presentinvention.

A stock solution of chloramine-T was first prepared by adding 47.5ounces (1204.854 grams) to one gallon of sterile water in a dark brown(light-resistant) container and the resulting solution mixed thoroughly.The solution was then filtered through a micropore filter into a secondlight-resistant (dark brown) container. The solution was then aliquotedinto light-resistant bottles, with each aliquot containing 10-20milliliters (mls).

93.553 grams of sodium bicarbonate were weighed out and added to 39.689grams of sodium chloride in a sterile mixing bowl. To this dry mixturewas added 3-6 mls of the chloramines-T stock solution, 1 milliliter (ml)of 3% hydrogen peroxide, and 30 milliliters of a solution containing3.63% (w/v) chlorhexidine gluconate, 3.64% (v/v) isopropyl alcohol,25.1% (w/v) poloxamer 237, 0.89%-0.99% (w/v) lauramine oxide), 2.14%(w/v) gluconolactone and 36.1 mg/L FD&C Red 40. The ingredients weremixed with a wooden ladle until the mixture was fully incorporated.

The resulting paste had a total volume of approximately 100 mls, and aweight of 6 ounces (170.01 grams). The mixture was stored in a tightlysealed, sterile, light-impervious porcelain container having a lid witha rubber seal.

A liquid rinse was made from the paste by adding 5 ml of paste to 50 mlof sterile water.

Example 2

Effect of a paste of the present invention on a pre-cancerous lesion ofthe lower lip of a patient treated iatrogenically with 5-Fluorouracil).The patient, an avid golfer with a lifetime of sun exposure, was on aCoumadin anticoagulation regime. The 5FU, had caused severe desquamationof the lip and uncontrollable bleeding (FIG. 3A). A paste made accordingto Example 1 was applied to the lesion daily (or bi-daily) for 10minutes per treatment (FIG. 3B), followed by application of vitamin E.After 27 days of treatment, the lesion was completely healed (FIG. 3C).

Example 3

Effect of a paste of the present invention on a diagnosed pre-cancerouslesion of the mid lateral aspect of the tongue. A 72-year-old femaleshowing confirmation of cancer with a second diagnostic vizilite testfor cancer (FIG. 4A). A paste made as described in Example 1 was appliedto the lesion for ten minutes daily, or on alternative days, for 27 day,after which the lesion was treated with Vitamin E oil. This treatmentresulted in complete remission of the lesion together with a loss of thehyperkeratotic tissue (FIG. 4C).

Example 4

Treatment of scar tissue containing antibiotic resistant bacteria (FIG.5A). A 67-year-old, white female, presented with a persistently drainingsinus and fistula, following facial surgery. Scar tissue from thesurgery was infected with a drug-resistant bacteria. A high-dosagespaste, prepared as described in Example 1 and using 6 mls ofChloramine-T, was applied to the scar tissue, 20 minutes perapplication, for 45 days. Following application of the paste, the scartissue was then treated with vitamin E oil. The above-describedtreatments resulted in closure of the fistula and complete healing ofthe wound (FIG. 5C).

Example 5

Treatment of facial acne using paste of the present invention.

A 44 year old Hispanic female presented with severe long term acnevulgaris on her face (FIG. 6-1). Paste prepared as described in Example1 was applied once to the acne lesions for 10 minutes. The result ofthis single application is shown in FIGS. 6B through 6D.

Example 6 Treatment of Third Degree Burn

A 66 year old white female presented with a third degree burn resultingfrom contact with hot wax. (FIG. 7A). Past, prepared according toExample 1 was applied b.i.d. for two weeks. Each application of pastewas followed by an application of vitamin E oil. This treatment regimeresulted in complete healing of the burn with minimal scarring. (FIG.7C)

Example 7

A retrospective study of 50 consecutive oral surgery patients (26males/24 females, all signing consents) were treated with either therinse or the paste or a collagen plug impregnated with the paste, andwere followed for post-operative complications, to include painindexing. The objective of this study is to observe the pain responseand complications to conventional surgical therapy, if any, of acomposition of the subject invention. The study was conducted at TheDental Connection in Key Biscayne, Fla.

In this retrospective study of 50 consecutive dental surgical patients,patients were monitored for the effects of a composition of the subjectinvention, prepared as a paste or rinse, and administered during surgeryor for post-surgical care. Patients aged 18 to 96 were given either arinse, paste and/or a collagen plug impregnated with the composition tothe surgical site, and were scored for post-operative pain. The testingprocess was progressive and un-blinded.

In the early stages of the study, a rinse to the wound or area wasapplied, later a rinse and paste and finally an impregnated sterilecollagen plug placed into the wound and left in situ, sutured inposition. Patients were assessed for pain the first day and then eachday, for up to 2 days. Each patient was asked to score pain as: 0=nopain, 1=mild pain, 2=moderate pain, and 3=severe pain. Pain killers wereprescribed, Ibuprofen 800 mgs. Q-6 hourly, or Percocet #5 325 mgs.

Patients were instructed to keep track of the amount of pain (using thedesignated 0-1-2-3 scale), the amount of pain killers taken and when.

Patients were also instructed to take 800 mgs of Ibuprofen or Ibuprofenas soon after surgery as possible and that, if pain was not controlledby these tablets, then to take 1 Percocet #5 325 mgs Q 2-3 hourly, untilthe pain was under control. Antibiotics were given routinely the nightprior to surgery and patients were asked to continue for 5 days. Alsoprobiotics (Jarro-dophilus or live yogurt) were prescribed to reduce theuntoward effects of the antibiotic therapy. Vitamin C 500 mgs. t.i.d.was also recommended to be taken 3 times per day for three weeks withmeals.

Cases involving the sinus and placement of implants were explored. Sotoo were large cysts solitary, apical and periodontal lesions, caused bychronic infections. Using socket preservation techniques then boneaugmentation using human or animal (cow) freeze dried mineralized bone,plus judicial use of membranes to re-grow alveolar bone, it was possibleto place implants. Wounds and surgical sites, infected and non-infectedwere used to put this substance through its paces. All surgicaltechniques used were standard accepted procedures. Some patientsreceived oral sedation using Triazolam 0.25 mgs or Diazepam 10 mgs atthe start of their procedures assisted with nitrous oxide and oxygenthrough a nose mask.

Summary of Results—50 patients: 26 males, 24 females (mean age of men44.8/women 51.9). The results of those patients male and female who hadsimple extractions and who had rinse/paste placed in the woundspost-operatively had virtually no pain post-operatively, took very fewpain killers and complained of very little post-operative pain.

Those male patients who had Collaplug impregnated with rinse/pastescored slightly higher on the pain index at 1.3 the first day with theCollaplug versus 0.75 without the Collaplug and the women with theCollaplug had 0.5 pain index on average and without the Collaplug 0.75pain index. Both male and female scoring at the minimum pain level wasremarkable for a first day post-operative pain score.

All patients both male and female complained of a pain index of 0.5 daytwo with or without the Collaplug. Regarding the group of males who hadsimple single extractions, teeth #15, #7, #8, #16 and who had the rinseplaced into the wounds post operatively and the paste placed to theclosed wounds, virtually no pain killers were used by this group and themembers experienced little to no post-operative pain.

Male Average Pain Female Average Pain 1^(st) Day = 0.68 1^(st) Day =0.875 2^(nd) Day = 0.36 2^(nd) Day = 0.3

Methods

Oral Surgery-Periodontics-Implants-Retrospective Study

-   -   (Pain Scale 0=None, 1=Mild, 2=Moderate, 3=Extreme)

MALES (n=26)−Average Age=44.8

-   -   A. Patient 044—66 y/o male

Problem: Fractured bridge #12 to #14-#12 cyst 10 mm×10 mm-cyst hadperforated sinus-heavy ETOH-bruxist-taking Plavix

First procedure—patient placed on Augmentin prior to surgery. Cut offbridge #14, raised flap #11 to #14. Sinus lift 6 mm window #12 siteBio-Oss, Bone & Bio-Gide membrane into sinus, Collatape to entry, freezedried mineralized bone to #12 after cyst enucleated, socketpreservation, Collatape impregnated with paste to cover membrane.

Second procedure—patient placed on Augmentin prior to surgery-12-15incision graft of attached gingivae-Straumann implant placed to #12 site4.8×12 mm R/N and #14 site 4.8×12 mm W/N-#14 root augmented withTetracycline, freeze dried mineralized bone and Bio-Oss-successfulresults.

Paste and rinse post-operative daily 3×/day for 4 days for eachprocedure-no complications reported.

-   -   Pain Score: 1^(st) Day=1—One ibuprofen 800 mgs, all day        -   2^(nd) Day=1−One Percocet 325 mgs (Oxycodeine)    -   B. Patient 051—67 y/o male

Problem: bruxist-overactive Thyroid condition-needs implants

First procedure—3i implants placed to #19 site 5/6×13 mm and to #20 site4/5×13 mm-no complications reported.

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0

Second procedure—Straumann implant placed to #2 site 4.8×10 mm W/N SLActive Ti-no complications.

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   C. Patient 038—47 y/o male

Problem: #18 severe infection, tooth fractured with large cyst 13 mm×15mm close to Inferior Dental Nerve-High ETOH

Procedure—enucleated cyst-osteograft (cow bone) placed-Collaplug withpaste and rinse-placed on antibiotics-no complications, minimal pain

-   -   Pain Score: 1^(st) Day=1.5        -   2^(nd) Day=0    -   D. Patient 042—19 y/o male

Problem: Multiple extractions

Surgical extraction of teeth #B, #C, #I, #5, #R, #Q, #N, #M, #L, #K

-   -   Pain Score: 1^(st) Day=1        -   2^(nd) Day=1    -   E. Patient 034—47 y/o male

Problem: Site regeneration then needs implants-lower right first-lowerleft second-multiple treatment surgeries-severe infections and severedecay-bruxist-smoker, one P/P/D-ETOH

First procedure—to each side, socket preservation-site regeneration-#30,#29-freeze dried mineralized bone

Second procedure—enucleated cyst 13 mm×15 mm on #19, #18 site-freezedried mineralized bone.

Third procedure—lower right, Straumann implant placed to #30 site 6.8×12mm W/N-freeze dried mineralized bone-Straumann implant placed to #28site 4.1×12 mm-freeze dried mineralized bone, CaSO₄.

Fourth procedure—lower left, Straumann implants placed to #18, #19 sites4.8×12 mm SP-3 bottles ½ gm each freeze of dried mineralized bone, CaSO₄plus membrane-antibiotics used Clindamycin 300 mgs, Amoxicillin 500 mgsfor 7 days, paste and Vitamin E-no complications

Post op: multiple visits paste and vitamin E-had a crack on left lip ithad crusted after surgery and caused pain

-   -   Pain Score: (from surgical sites) 1^(st) Day=0        -   2^(nd) Day=0    -   F. Patient 025—76 y/o male

Problem: #15 super erupted needed extraction-bipolar-no pain threshold

Procedure—surgical extraction of tooth #15-Collaplug impregnated withpaste-no antibiotic needed-no complications

Post-op: Ibuprofen 800 mgs stat-5:00 p.m. 2 Extra-Strength Tylenol-8:00p.m. Ibuprofen 800 mgs.

-   -   Pain Score: 1^(st) Day=0.5 (virtually no pain)        -   2^(nd) Day=−1    -   G. Patient 037—70 y/o male

Problem: needs multiple implants and sinus grafts-long history of sinusinfections (since 14 years of age)-poor health-multiplemedications-severe clencher/bruxist-severe decay-cracked toothsyndrome-high BP-Diabetes-PSAIII

First procedure—#30 immediate extraction and placement of Straumannimplant 4.8 mm bone level-paste and irrigation and placement of freezedried mineralized bone.

Average Pain index 1^(st) Day=1.5—1 Ibuprofen, 2 Tylenol #3, Ibuprofen

-   -   Pain index 2^(nd) Day=0

Second procedure—#14 extracted, sinus perforation repaired withBiomend-socket preservation ½ gm freeze dried mineralizedbone-Clindamycin 300 mgs three times a day for 5 days plusJarro-dophilus probiotics

Post-op: 1 Ibuprofen 800 mgs stat

Post-op complication: dry socket, placed on vitamin C 1000 mgs threetimes a day for three weeks-good resolution

Pain index 1^(st) Day=1—2 Tylenol #3, Ibuprofen before bed, fever brokeat 1:30 a.m.

-   -   2^(nd) Day=1—1 Ibuprofen 800 mgs

Third procedure: —#15 Sinus tap and Straumann implant, Bio-Oss, 4.8×10mm B/L

Pain index 1^(st) Day=2.5

-   -   2^(nd) Day=2

Fourth procedure—#14 extraction and immediate placement of Straumannimplant 4.8×10 mm TE-perforation of sinus repaired with paste plusCollaplug, Collatape, freeze dried mineralized bone and CaSo4

Post-op—placed on Vitamin C 1500 mgs three times per day, paste appliedto mouth and nose

Pain index 1^(st) Day=1.

-   -   2^(nd) Day=0

Problem: against medical advice patient decided to leave town for onemonth and returned with raging sinus infection and suppurating pus.Placed on Clindamycin 300 mgs and metronidazole 500 mgs t.i.d.×10days-rinse, paste to mouth and nose (6 minutes) daily for 10 days-a badsituation with a successful conclusion.

#3 fractured-palatal root caries and separated from crown-wants to delayimplant surgery as has many serious commitments

Fifth procedure—surgical removal of roots-severe perio defect on#2-socket preservation with MinerOss, Bio-Gide membrane and Collatapewith paste-antibiotic Clindamycin 150 mgs three times a day for 10 daysand metronidazole 500 mgs three times a day for 10 days-paste for 10minutes, mouth rinse-Success!!

Pain index 1^(st) Day=0

-   -   2^(nd) Day=0

Sixth procedure—Extraction #4 and immediate placement of Straumannimplants to #3 site 4.8×10 mm W/N TE and #4 site 4.1×10 mm R/N TE withCaldwell Luc sinus lift, Bio-Guide, Bio-Oss. Tear to membrane repairedwith Bio-Mend-paste and Vitamin E-stopped antibiotics due to stomacheven though taking probiotics-no complications this time.

Pain index—1st day=0—1 Ibuprofen 800 mgs

-   -   2nd day=1    -   3^(rd) day=less than 1    -   4^(th) day=less than 1        -   Aggregate Pain Score: 1^(st) Day=1.2            -   2^(nd) Day=0.2    -   H. Patient 026—79 y/o male        Problem: needs tooth #8 extracted and immediate partial        placed-no pain threshold        Procedure—uncomplicated surgical extraction tooth #8 and        placement of immediate partial-Collaplug with paste and        irrigation with rinse    -   Pain Score: 1st Day=1        -   2^(nd) Day=0.2    -   I. Patient 035—80 y/o male

Problem: #18, #19 failed implants-difficult case-heart valvereplacement-Coumadin-bruxist-very strong bite

First procedure—tried to salvage implants in #20, #21 sites, flapTetracycline 2 minutes, paste and freeze dried mineralized bone withCaSo4 and membrane

Pain index—1^(st) Day=0

-   -   2^(nd) Day=0

Second procedure—removed failed implants to #20, #21 site-Amoxicillin,freeze dried mineralized bone, Bio-Mend membrane for socket preservation

Pain index—1^(st) Day=0

-   -   2^(nd) Day=0

Third procedure—#4 extracted and augmented with freeze dried mineralizedbone along with immediate placement of Straumann implant to site #44.8×12 mm B/L

Pain index—1^(st) Day=0

-   -   2^(nd) Day=0

Fourth procedure—#21 site Tetracycline 2 minutes-freeze driedmineralized bone and Bio-Mend-Straumann implant placed to site #214.8×12 mm, wound irrigated with paste, Amoxicillin, 2 extra-strengthTylenol.

Pain index—1^(st) Day=0

-   -   2^(nd) Day=0

Fifth procedure—#21 implant uncovered-removed granulation

Pain index—1^(st) Day=0

-   -   2^(nd) Day=0

Sixth procedure—#14, #13 extractions and immediate placement ofStraumann implants #14, 4.8×10 mm TE-#13 4.1×12 mm TE-Augmentin-sinusperforation, rinse and paste to wounds, freeze dried mineralized bone-nocomplications

Pain index - 1^(st) Day = 0 Aggregate Pain Score: 1^(st) Day = 0 2^(nd)Day = 0 2^(nd) Day = 0

-   -   J. Patient 047—18 y/o male

Problem: 4 very difficult impacted wisdom teeth (10/10difficulty)-mesio-angular low involving nerve in the lower left sideworst-upper #1, #16 high hooked roots and splayed.

Procedure—surgical extraction of #1, #16, #17, #32-2 Extra-StrengthTylenol one hour prior to appointment-Collaplug with rinse-photostaken-daily rinses 8.6.10 through 8.13.10.

-   -   Pain Score: 1^(st) Day=2        -   2^(nd) Day=1    -   K. Patient 050—62 y/o male

Problem: #8 cyst 8 mm×7 mm

Procedure—apicectomy #8-freeze dried mineralized bone-Tetracycline withCaSo4 membrane-paste and rinse to the wound-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   L. Patient 033—90 y/o male

First procedure—2 Extra-Strength Tylenol prior to procedure-surgicalextractions of teeth #19, #20, #22 and immediate placement of Straumannimplants to #19 site implant 12 mm W/N Plus, to #20 site 10 mm R/N Plus,to #22 site 12 mm R/N Plus-wounds irrigated with rinse-paste applied towounds along with freeze dried mineralized bone-very hard bone-playedtennis day after procedure.

-   -   Pain Score 1^(st) Day=3        -   2^(nd) Day=2

Second procedure—#9 surgical extraction and immediate placement ofimplant-no complications

-   -   Pain Score 1^(st) Day=0        -   2^(nd) Day=0

Third procedure—#30 extraction and immediate placement of Straumannimplant 4.8×10 mm plus freeze dried mineralized bone with paste andrinse-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   M. Patient 041—19 y/o male

Problem: #1, #16, #17, #32 deep impacted wisdom teeth (9/10difficulty)-roots partially formed-uppers high

Procedure—Amoxicillin-2 Extra Strength Tylenol-#1, #16, #17, #32extracted-Collaplugs plus paste-rinse to wounds after extractions-nocomplications

-   -   Pain Score: 1^(st) Day=1        -   2^(nd) Day=1    -   N. Patient 048—39 y/o male

Problem: Severe bone loss #14-sinus perforation-MarfansSyndrome-anti-coagulants

Procedure—#14 socket preservation-augmentation-Collatape paste andrinse, freeze dried mineralized bone, hypoglycemic, sugar given. Rinseto site, mouth and nose. Augmentin 875 mgs for 6 days, probiotics-nocomplications

-   -   Pain Score: 1^(st) Day=1        -   2^(nd) Day=0    -   O. Patient 040—18 y/o male

Problem: wisdom teeth 7.5 out of 10 difficulty

Procedure—#1, 16, 17, 32 surgical extraction-Amoxicillin-2extra-strength Tylenol one hour prior to surgery-sedation-Collaplug pluspaste/rinse-paste to close wounds

-   -   Pain Score: 1^(st) Day=1.5        -   2^(nd) Day=0    -   P. Patient 046—18 y/o male

Problem: Wisdom teeth-#16 palatal very high=9/10 difficulty-#1, #17,#32=7/10 difficulty

Procedure: #1,16,17,32 surgical extraction-2 extra-strength Tylenol Onehour prior to surgery-Collaplug plus paste into wounds-uppers noCollaplug only rinses with paste-all sockets irrigated with paste-nocomplications

-   -   Pain Score: 1^(st) Day=2        -   2^(nd) Day=1.5    -   Q. Patient 027—35 y/o male

Problem: #16 super erupted

Procedure—surgical extraction #16-2 Extra strength Tylenol one hourprior to surgery-Collaplug plus paste-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   R. Patient 043—49 y/o male-heavy smoker-over weight-high stress        lifestyle-constantly having to fly because of business        commitments-poor compliance

Problem: very difficult wisdom teeth (12/10)-high risk nerveinjury-needs++bone removal-deep impaction

Procedure—#17, #32 surgical extraction-Collaplug-no paste-Amoxicillin-2extra-strength Tylenol-Percocet

Post-op: numbness lower left tongue-patient said had to fly to England,against medical advice-developed dry socket and dysthesia InferiorDental Nerve-treated with Vitamin C 1 gm q.i.d-paste into socket-treatedwhilst constantly flying in and out of town to South America/Europe-poorcompliance, heavy drinking, smoking Patient got secondary osteomyletisinfection from South American trip-after detection of osteomyelitis wasplaced on Clindamycin told patient had to get serious, stop smoking anddrinking, said had to fly to Argentina that night (7 Hours) and to flyback tomorrow (7 hours). Patient improved but lost patient to follow up.

Post-op: Developed Osteomyelitis

-   -   Pain Score: 1^(st) Day=1        -   2^(nd) Day=1    -   S. Patient 049—26 y/o male

Problem: trauma case-severe lacerations to lower lip through andthrough-wound untreated for eight hours post trauma-#24, #25 teethreplaced after being out for one hour although kept moist-high risk ofsuppuration

Procedure—#26 tooth lingually intruded-paste and rinse-high risk ofsuppuration-area cleaned well with paste and rinse-drain placed intolower lip-teeth washed with rinse-lingual splint to hold teeth inposition-also noted green stick fracture of mandible through #19, notreatment-tetanus shot-drain removed next day-paste applied

-   -   1) One month later (30 days) teeth #24, 25, 26 root canal        treated    -   2) Lingual splint removed after 21 days-great result, no side        effects-no complications        -   Pain Score: 1^(st) Day=0            -   2^(nd) Day=0    -   T. Patient 039—30 y/o male

Problem: #17, #32 very difficult disto-angular large teeth-condylarhyperplasia-difficult extractions-Inferior Dental Nerve involved

Procedure—#17, #32 extracted-nerve involvement-left side neededextensive bone removal-Amoxycillin-Ibuprofen 800 mgs-Percocet-Collaplugplus paste

Post-op: left side lingual dysthesia with long term discomfort-post-opdry socket-left side irrigated with paste and rinse-Clindamycin 500 mgst.i.d. for 7 days.

Second procedure—one month later-secondary surgery to remove dead bonefragments, 3 mm×1 mm sitting on nerve-paste and rinse-Clindamycin-followup visits for paste and rinse-no further problems-lingual dysthesiatotal improvement

-   -   Aggregate Pain Score: 1^(st) Day=1        -   2^(nd) Day=1.5    -   U. Patient 029—96 y/o male

Problem: #9 needs extracting-poor health-high blood pressure-frail-bonelike hard cheese and brittle

Procedure—#9 extracted-2 pieces-Straumann implant placed to #9 site BL4.8×RC 12 mm W/N-freeze dried mineralized bone-rinse afterdrilling-blood pressure 150/105-control of blood pressure poor did nottake medications-good result-no complications

-   -   Pain Score—1^(st) Day=3, later that day 1        -   2^(nd) Day=1    -   V. Patient 032—62 y/o male

Problem: #13 tooth fractured-close to sinus-tooth had bad smell-allergyto Iodine-Clindamycin 300 mg t.i.d.×7 days-

Procedure—#13 tooth extracted-rinse to socket-Straumann implant placedto #13 site drilled B/L 4.1×12 mm RC-plus freeze dried mineralizedbone-Percocet and Ibuprofen prescribed along with probiotics(jarro-dophilus) and Vitamin C 3 times a day for three weeks no problemsup to and including third day with paste and rinse-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   W. Patient 036—40 y/o male

Problem: Severe bruxist-chronic sinusitis-infected tooth#15-Z-Pack-Percocet-Ibuprofen-2 Extra Strength Tylenol

Procedure—#15 extracted and implant placed-tooth infected-long term hugesinus communication-irrigated wound and sinus with rinse-Biomendmembrane to sinus floor parachute style-freeze dried mineralized boneand CaSo4 primary closure over implant (palatal root)-post op sinusrinse, mouth rinse-no post op problems, says first time that he canremember has not had sinus problems-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   X. Patient 030—38 y/o male

Problem: severe caries #9

Procedure—#9 extracted and immediate placement of Straumann implant4.8×10 mm B/L-Clindamycin-Ibuprofen 800 mgs-freeze dried mineralizedbone and paste to wound and socket plus Vitamin E-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   Y. Patient 031—53 y/o male

Problem: severe caries #30-Clindamycin 300 mgs t.i.d.×7 days

Procedure—#30 surgical extraction roots-placed Straumann implant to #30site 4.8×12 mm TE-Percocet-=Vitamin C 500 mgs t.i.d

Post-op: side effect to Percocet D/C-used extra strength Tylenol×7days-may have problems with ibuprofen but took one ibuprofen withoutproblems-alternative days rinse and paste-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   Z. Patient 028—23 y/o male

Problem: #30 failed root canal-ETOH alcoholic

Procedure—#30 failed root canal-surgical extraction-Collaplug withpaste-no problems post op-wanted more Percocet (addict)-no complications

-   -   Pain Score: 1^(st) Day=1        -   2^(nd) Day=0

FEMALES×24−Average Age=51.9

-   -   AA. Patient 020—23 y/o female

Problem: very difficult wisdom teeth-mesio angular #17 very close tonerve-deep bony tooth impaction (10/10) high risk-#32 hooked roots

Procedure—#1,16,17,32 extractions-#17, #32 Collaplug with paste-#1, #16paste and irrigation only-also took antibiotics, probiotics-onlycomplication swelling of lower lip-low pain

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=1    -   BB. Patient 005—75 y/o female

Problem: #30 unsalvageable-hyper allergic, 12 medications-allergies to11 drugs-heavy bruxist-dental phobic-no pain threshold-antidepressants

Procedure—#30 immediate extraction mesial root and placement ofStraumann implant to #30 site SP 4.8×10 mm W/N Ti-freeze driedmineralized bone-rinse after drilling-paste placed two minutes aftersurgery-several follow up visits (3)-paste and Vitamin E for 2minutes-no complications

-   -   Pain Score: 1^(st) Day=3        -   2^(nd) Day=0    -   CC. Patient 022—56 y/o female

Problem: #3 unsalvageable-alcoholic-stopped smoking

Procedure—Multiple surgeries—

-   -   1) #3 surgical extraction-socket preservation-rinse after bone        removal-freeze dried mineralized bone and CaSo4    -   2) sinus lift #2, #3-rinse after bone removed-Bio-Oss-placed        Straumann implant 4.8×10 mm WN-window covered with Ossix        membrane-on antibiotics Augmentin 875 mgs. B.D.    -   3) #15 sinus lift-Bio-Oss-Bio-Gide-Ossix membrane to furca-rinse        after bone removal    -   4) apicectomy #24, #25-Amoxycillin 500 mgs-freeze dried        mineralized bone plus collatape-rinse after bone removal    -   5) #4 implant placed 5.18.07 to 3.05.10 mobile-7 mm bone        loss-may have done loading of implant/sinus graft too        early-treatment to resuscitate implant-flap, tetracycline 2        minutes-paste 5 minutes-tetracycline rinse-Bio-Oss plus CaSo4        membrane-paste over wound-antibiotics Clindamycin 300 mgs        t.i.d.×10 days, Metronidazole 500 mgs.×10 days-rinse daily from        5.21.10 to 6.29.10-good result success-no complications        -   Average Pain Score: 1^(st) Day=0            -   2_(nd) Day=0    -   DD. Patient 010—47 y/o female

Problem: severe decay multiple teeth (6)-granulation tissue++++-historyof drug abuse and alcohol-no pain threshold

Procedure—Multiple extractions—

-   -   1) -#14, 15, 17, 18 surgical extractions-Collaplug with        paste-post-op-Amoxycillin-Percocet-Ibuprofen 800 mgs.-Vitamin C        500 mgs-minimal pain    -   2) #3,5-Clindamycin antibiotic-surgical extraction-patient very        agitated-placement of implant into #5 site and removal of        granulation tissue with freeze dried mineralized bone, (Bio-Oss        or cow bone)-bone also #3 site (Bio-Oss)-then Collaplug with        paste and rinse to wound communication into sinus        -   Pain Score: 1^(st) Day=2            -   2^(nd) Day=0    -   EE. Patient 006—69 y/o female

Problem: severe perio disease generally-#31, #32 deep bone loss, mobileteeth-Thyroid disease-Herpes++++

Pre-op: Clindamycin and Metronidazole-Vallium-Extra-strength Tylenol

First Procedure—#30, #32-surgical extraction-removal of granulationtissue+++++-freeze dried mineralized bone-Collaplug with paste-placementof Straumann implant into #30 site 4.8×10 mm W/N

Post-op: active outbreak of herpes simplex vesicles, Zovirax ointmentand Valtrex tablets

Second Procedure—Biopsy upper left soft palate-rinse and paste-Valtrex,Zovirax, Clindamycin and Metronidazole, for pain Percocet-Vitamin C

Third Procedure—Treatment for severe perio disease

-   -   1) deep scale and curettage with irrigation of rinse/paste    -   2) antibiotics Clindamycin 300 mgs and Metronidazole 500 mgs for        10 days    -   3) occlusal adjustment

Resounding resolution—pocket depths went from 7 mm and 5 mm to 3 mm withteeth non mobile-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   FF. Patient 009—44 y/o female

Problem: #30 severe pain-flying day after planned surgery

Procedure—#30 extraction with removal of bone-Collaplug with paste-1Ibuprofen 800 mgs after surgery-2 Percocet 1 before bed-no complications

-   -   Pain Score: 1^(st) Day=1        -   2^(nd) Day=0.5    -   GG. Patient 008—68 y/o female

Problem: #30 needed extraction-no painthreshold-ETOH-antidepressant-very sensitive tissues-bruxist-reaction toSeptocaine-diagnosed with arthritic condition which breaks downbone-Amoxycillin 500 mgs t.i.d.×10 days

Procedure—#30 extracted and immediate 3i implant 5×13 mm placed to #30site-very brittle++++bone removed-freeze dried mineralized bone-Ossixmembrane and CaSo4-Ibuprofen 800 mgs-Tylenol #3 (20)-5 days for pain todecrease-added own mix of colloidal silver and aspirin to wound alongwith pain killers Tramadol

50 mgs-developed hives with Tramadol pain killer-difficult managementcase-no complications with surgery

-   -   Pain Score: Minimal with pain-killers taken    -   HH. Patient 013—38 y/o female

Procedure—minor surgery for epulis removal-paste and Vitamin E-no pain,no post op complication “have you done the surgery?”-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   II. Patient 015—18 y/o female

Problem: wisdom teeth extraction 7/10 difficulty-Turner's Syndrome

Procedure—#16, #32 surgical extraction-rinse and paste-antibiotics-nocomplications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   JJ. Patient 014—38 y/o female

Problem: hyper thyroidism-4 months pregnant-difficult extraction #30long bulbous roots-2 extra strength Tylenol

Procedure—#30 surgical extraction-socket preservation-freeze driedmineralized bone and CaSo4-great result-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   KK. Patient 011—51 y/o female

Problem: ETOH abuse-drug abuse-epi sensitivity-no pain threshold-12/10difficulty-high BP-full mouth reconstruction-severe perio disease-highcosmetic case-huge graft dermis Allograft, Emdogain, Miner-Oss bone

First procedure—upper perio flap #2-#6 prep gel and Emdogain to #4 #5.Prepared receptor site #4, sinus elevation TAPP Straumann implant placedto #4 site 4.1×8 mm TE, Allergan over #4 and #5 sites. Facial flap #14,#15 split thickness #12-#13 #14 removed, #12, #13 placed Emdogain-placedStraumann implant to #14 site 4.2×8 mm TE-sinus TAPP Allergan, paste andrinse

Second procedure—Split thickness flap #18-#31, osteotomy site #19, #20,#30 placed Straumann implants to #19, #30 4.8×10 mm W/N and to #204.1×10 mm TE, prep gel to #21-#29 Emdogain-bone contouring and Miner-Ossto sockets-limited irrigation of paste

Post-op: patient very difficult management, no compliance and woundsopened up-had to re-suture twice, finally placed tape across chin tostop flap being pulled open.

Paste was the only salvation-patient returned for rinse and paste3.15.11 to 3.17.11; 3.18.11-3.21.11; 3.24.11-finally adhesion 4.21.11

Third procedure—failed implant #14 site, no sinus graft formation, sinusinfected, irrigated with rinse-placed Collaplug and paste, freeze driedmineralized bone primary closure-successful graft and new implant site

Fourth procedure—#12 perio breakdown, Tetracyline and paste 2 minutes,Clindamycin. Failed implant #20/21-flap #19 to #23 removed #20 and #21new Straumann implants 4.1×10 mm, freeze dried mineralized bone plusBiogide-paste applied 8.8.11, 8.11.11.

Post-op: lost patient-went to have completion of case elsewhere-lastseen area was healing well and surgical sites healed ONLY AS A RESULT OFTHE PASTE!!!!!!

-   -   Aggregate Pain Score: 1^(st) Day=3        -   2^(nd) Day=2    -   LL. Patient 021(A)—58 y/o female

Problem: needs sinus grafts to upper right and upper left sites-highBP-Synthroid for Thyroid-addicted to Nicorette-non stop motion ofmouth-labile mood wings

First procedure—sinus grafts upper right #12 position and upper left#14, #15 position-flaps #1-4 and #13-16-Bio-Oss 2 gms-rinse to Osteotemysites and sinus-Ossix membranes

Second procedure—surgical #2, #14, #15-flaps #1-3, #13-16 Straumannimplants placed into #2 site 4.8×10 mm W/N, into #4 site 4.8.×10 mm B/LRC, into #15 site 4.8×10 mm W/N rinse to osteotomy and sinus-goodresult-no complication

-   -   Pain Score: 1^(st) Day=1.5        -   2^(nd) Day=0    -   MM. Patient 003—86 y/o female

Problem: tooth #8 tooth avulsed-Clindamycin-long-term severely infectedsite granulation tissue+++++

Procedure—placement of Straumann implant into #8 site 4.8×12 mmB/L-copious paste and irrigation-no complications

Post-op: Clindamycin caused problem

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   NN. Patient 019—21 y/o female

Problem: Extract wisdom teeth (5/10) difficulty

Procedure—#1,#16,#17,#32 surgical extraction-Amoxcillin 500mgs-Collaplug with paste to lower #17, #32 and rinse to #1,#16-Ibuprofen 800 mgs-Percocet-no complications

-   -   Pain Score: 1^(st) Day=2        -   2^(nd) Day=1    -   OO. Patient 023—56 y/o female

Problem: full mouth reconstruction-thyroiddisease-antidepressants-dental phobic

First Procedure—Graft I-periodontal surgery with facial split thicknessflap #3-#14-roots had EDTA 17% 2 minutes-Emdogain-Alloderm graftmaterial-paste to wound and flap

Post-op: 1) Flap came loose and re-sutured the nextday-paste+irrigation.

2) Flap loose again, re-sutured-paste and rinse-exposed graft material,paste applied to exposed material (Alloderm) #3,4,5 region and left onwound for 10 minutes-antibiotics Z-Pack-Ibuprofen 800 mgs-2 daysbetter-flying out of town not good-review when returned after 12days-paste applied area healing slowly-past and rinse+Vitamin E GraftII-#9-#11 position-flying again-die back of flap-paste and rinse andantibiotics-re-closed graft (Alloderm) after wound opened with paste.Complained of pain, tension sutures removed, pain went-good finalresult-incredible regenerative ability of paste

-   -   Pain Score: 1^(st) Day=3        -   2^(nd) Day=0    -   PP. Patient 012—70 y/o female

Problem: Extract teeth #21, #27-anti depressants-Thyroid disease-highBP-high Cholesterol

Procedure—extracted teeth #21, #27 and immediate placement of Straumannimplants to sites #22, #27 4.1×12 mm TE-freeze dried mineralizedbone-Collaplug with paste to #24, #25 area-Clindamycin 300 mgs t.i.d.×7days

Post-op: complained of chest pain-called EMS-EKG normal-heart problemsruled out-said cause of problems gastric reflux from Clindamycin whichwent away after cessation of Clindamycin-great result

-   -   Pain Score: 1^(st) Day=2        -   2^(nd) Day=0    -   QQ. Patient 007—90 y.o female

Problem: needed #12, #13 extracted-(sick lady) pace maker-high BP-kidneyinfection-high cholesterol-thyroid disease-anticoagulantWarfarin-depression

Procedure—#12, #13 surgical extraction-partial loose due to loss of #12,#13-Straumann implant placed to #11 site×10 mm W/N and zest anchorsplaced to #11 position-freeze dried mineralized bone-rinse and pasteapplied to wound and implant site-control of PT/PTT-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   RR. Patient 018—29 y/o female

Problem: upper wisdom teeth fully erupted 5/10 difficulty-cysticfibrosis

Procedure—#1, #16 surgical extraction-rinse-paste-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   SS. Patient 017—22 y/o female

Problem: all wisdom teeth extraction-difficulty 6/10-diabetesinsipidous-Ibuprofen 800 mgs-Percocet-Diazepan-2 extra strength Tylenol

Procedure—#1, #16, #17, #32 surgical extraction-paste-rinse-noproblems-no complications

-   -   Pain Score: 1^(st) Day=1        -   2^(nd) Day=1    -   TT. Patient 016—35 y/o female

Problem: 3 wisdom teeth need extraction-#1 palatal impaction-#17 100%impacted against #18

Procedure—#1, #17, #32 surgical extraction-#17 Collaplug withpaste-paste irrigation follow up

Post-op: complained of bad taste and dry socket discovered-pain camefrom tooth #2 (endodontic abscess) to go to Argentina for root canal andimplant

-   -   Pain Score: 1^(st) Day=2        -   2^(nd) Day=2    -   UU. Patient 001—46 y/o female

Problem: multiple extractions-smoker-sugarholic-idiopathicthrombocytopaenia-on prednisone

First procedure—#23, #26, #30 surgical extractions-Collaplug withpaste-no complications

Second procedure—#2, #3, #5, #13, #15 surgical extractions-Collaplugwith paste-no complications

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0    -   VV. Patient 021(B)—62 y/o female

Problem: extract all remaining lower teeth

First procedure—#22-#27 surgical extraction placement of implants×8 tolower jaw-4 implants to #18,#19,#20,#21 sites and 4 implants to#37,#28,#29,#30 sites-fractured all rotatory instruments as bone likestone-immediate loading with lower full reconstruction

-   -   Pain Score: 1^(st) Day=0        -   2^(nd) Day=0

Second procedure—surgery re solitary bone cyst lower left area-cystsize=11.25×18.75-loss of sensation (left inferior dental nerve)-pasteand rinse-sensation returned after 3 months

-   -   Pain Score: 1^(st) Day=0 (dysthesia)        -   2^(nd) Day=0

Summary of Cases by Similar Procedures

24 Female subjects Extractions (001) Multiple #23, #26, #30Extractions + (002) Sinus Grafts #3, #14 Extractions + (003) (004) (005)(006) (007) (008) Immediate #8 #8, #9 #30 #30 #12 #30 ImplantExtractions + (009) (010) Collaplug + paste + #30 severe #14, #15, #17,#18, #31, #32 Immediate implant infection severe periodontitisExtractions + (011) (012) Immediate #4, #14, #19, #30 #22, #23, #24,#25, #26 Implant + sinus Emdogain allograft #27, #28 implants toGrafts + alloderm #4-#13, #20-#29 sites #22, #27 collaplug + Large softtissue paste to extraction sites Grafts Epulis (013) Removal #9, #10region Extractions + (014) Socket #30 Preservation + FDMB + CaSo4Extractions (015) (016) (017) (018) Wisdom teeth + #17, #32 #1, #32 #1,#16, #1, #16 cystic paste + rinse #17, #32 fibrosis Extractions (019)(020) Wisdom teeth + #1, #16, #1, #16, collaplug + #17, #32 #17, #32paste Electro- (021) Surgery upper #6, #11 Implant salvage (022)Tetracycline + #4/#5 site Paste + rinse implant Allografts & (023)Emdogain #3-#14, #7 graft Untethered due to talking, re-sutured Traumalower (024) Lip, tissue tear Thru & thru

26 Male subjects Extractions + (025) (026) (027) Paste + rinse #15 #7,#8 #16 Extractions + (028) Collaplug + #30 Paste Extractions + (029)(030) (031) (032) (033) Immediate #9 #9 #30 #13 #19, #20, #22 Implant +#9 Grafting (034) #19, #20, #28, #30 +  (035) bone graft for #4 +implant large cyst #22 + implant Exractions + (036) (037) Sinus graft +#15 #2 Immediate implant Extractions (038) (039) (040) (041) (042)Wisdom teeth + #18 #17, #32 #1, #16 #1, #16 #1, #16 rinse + pastesequestectomy #17, #32 #17, #32 #17, #32 long healing period (043) (045) #17 #1, #16 osteomyelitis-long #17, #32 recovery, smokerExtractions (046) (047) Wisdom teeth #1, #16, #1, #16 collaplug + paste#17, #32 #17, #32 left in wound Removal of (048) Tissue, #14 ExternalResorption + paste Avulsion of teeth (049) & tissue laceration #24, #25,#26 rinse + paste tissues of lips, lower jaw Apicectomy + (050) rinse +paste #8 Cystic #12 (044) & implants #12, #14

Females Pain Scores Pain Scale 0 = None, 1 = Mild, 2 = Moderate, 3 =Extreme 24 Females-Average Age = 51.9 Average Pain Day 1 = 0.875, Day 2= 0.3 No. Female's Age Record of Pain Day 1 Day 2 001 46 0 0 002 61 0 0003 86 0 0 004 82 0 0 005 75 3 0 006 69 0 0 007 90 0 0 008 68 0 0 009 441 0.5 010 47 2 0 011 51 3 2 012 70 2 0 013 38 0 0 014 38 0 0 015 18 0 0016 35 (pain from abscess on another 2 2 tooth) 017 22 1 1 018 29 0 0019 21 2 1 020 23 0 1 021 58 1.5 0 022 56 0 0 023 56 3 0 024 63 0 0

Males Pain Scores 26 Males-Average Age = 44.8 Average Pain Day 1 = 0.69,Day 2 = 0.38 No. Male's Age 025 76 0.5 −1 026 79 1 0 027 35 0 0 028 23 10 029 96 0 0 030 38 0 0 031 53 0 0 032 62 0 0 033 90 0 0 034 47 0 0 03580 1 0 036 40 0 0 037 70 0 1 038 47 1.5 0 039 30 1 1.5 040 18 1.5 0 04119 1 1 042 15 1 1 043 49 1 1 044 17 1 0 045 19 0 0 046 18 2 1.5 047 18 21 048 39 1 0 049 26 0 0 050 62 0 0

Results

In the more major surgical cases—extractions and immediate placements ofimplants, 9 females, 9 males, pain the first day scored on average formales 0.375 Day One and 0.375 Day Two. For females 0.71 Day One and 0.25Day Two. Only one male patient (90 years of age) complained of pain a2-3 the first day, 2 the next day but did not take any painkillers andplayed tennis the next day following three immediate extractions and 3implant placements. In the wisdom teeth cases—the more difficultextractions complained of normal swelling post-op. In the rinse/pastecases, 8 males scored with Collaplug 1.3 on Day One and 0.5 Day Twowithout Collaplug 0.75 on Day One and 0.5 on Day Two. 7 females painscored with the Collaplug 0.5 on Day One and 0.5 on Day Two and withoutthe Collaplug 0.75 on Day One and 0.2 on Day Two.

One difficult extraction in 1 male, tooth #17, (043) who was also aheavy smoker and two very difficult extractions, teeth #17, #30 (039)developed complications which resulted in second surgical procedures toremove some dead bone and subsequent antibiotic therapy (Clindamycin).They both complained of discomfort that was long term and lasted forthree to four weeks. Only one female (016) complained of chronic painfollowing surgical removal of teeth #1, #32. After further radiographicexamination her pain was associated with an abscess in tooth #2, notrelated to the surgery. She returned to Argentina for removal of thetooth and placement of an implant into the #2 site.

In those patients who had the Collaplug and paste and had all fourwisdom teeth removed or had simple extractions plus Collaplug/paste, 3males, 3 females it was noted a slightly higher pain index in only themales who had the Collaplug when compared to just the rinse and thepaste alone. In the females subset there was no difference in pain indexbetween the Collaplug and the rinse and paste. Those patients hadvirtually no pain at all, score 1 to 2 the first day and only 1 thesecond day with taking only 1 or 2 Ibuprofen 800 mgs the first day and 1800 mgs Ibuprofen the second day.

In those cases of sinus grafts or sinus grafts and implants (2females-002 & 011) (2 males-036 & 037) only one female patient (2 sinusprocedures, 1 extraction and 2 immediate implants 011) complained ofdiscomfort post-op. Ranging at the level of 3. In this case (011)Emdogain plus allograph (Alloderm) was placed from #29 to #20 with fullsurgical mobilization of the upper anterior mucosa, this becameun-tethered. The grafts were re-sutured (011) twice without furthercomplications although one implant was lost and re-grafted with minimumpain scored.

A second female patient (023) who also had full arch periodontalgrafting from #4 to #20, (Emdogain and allograft (Alloderm)) plus athird patient (002) who had two sinus grafts. The upper anterior mucosabecame un-tethered, resulting in one or two more attempts to resuturethe mucosa back. All the three female patients had a propensity to talkand the talking had dislodged the sutures. The rinse and paste givendaily was the only salvation and allowed all grafts to be salvaged andended up with very good cosmetic results.

All grafting materials Alloderm, Bio-Guide, Ossix membrane, Bio-Mend,Collatape, Collaplug, Bio-Oss, Miner-Oss, Freeze Dried Bone and implantsmade by Straumann and 3i were facilitated by the use of the rinse andpaste. To the extent that one patient (022) had a loose implant salvagedusing Tetracycline etch to clean up the implant surface and the pasteused to heal the ailing site. One patient (021B) had eight immediateimplants placed plus multiple extractions plus lower immediate full archreconstruction successfully with little to no pain at all.

An apicectomy on #8 in one male and two cases of trauma involvingavulsion of teeth and severe tissue lacerations, one male (049) and onefemale (024) were treated successfully with the rinse/paste without muchsurgical pain recorded and great results

One case of electrosurgical tissue removed (013) and other minorsurgical corrections were conducted using the past/rinse without anypost-surgical discomfort.

CONCLUSION

Use of the paste/rinse reduced the occurrence and discomfort of paindramatically in most surgical patients. The patients who had extractionsand were irrigated with the rinse/paste had the least pain of all, aswell as the fewest number of complications. The results from this studyindicate that the adjunctive use of both the rinse in the wound and thepaste post-operatively make a considerable difference to the painpost-operatively and reduced suffrage and post-operative complicationsto the vast majority of patients. It was noted that the pain killingeffect lasted up to two days or 48 hours post placement in the wounds.

What is claimed is: 1-12. (canceled)
 13. A therapeutic compositioncomprising: a) a chloride salt; b) a source of bicarbonate; and c) asource of hypochlorite; wherein the amount of the salt in thecomposition is sufficient to render the composition hypertonic; and,wherein the composition is alkaline.
 14. The composition of claim 13,wherein the concentration of the chloride salt in the composition is atleast 200 mM; the concentration of the source of bicarbonate in thecomposition is at least 4.9M; the concentration of the source ofhypochlorite is at least 0.5% (w/w).
 15. The therapeutic composition ofclaim 13, wherein the concentration of salt in the composition is in therange of from about 4M to about 8M.
 16. The composition of claim 13,wherein the chloride salt is selected from the group consisting ofsodium chloride and potassium chloride.
 17. The composition of claim 13,wherein the source of bicarbonate is selected from the group consistingof sodium bicarbonate, calcium bicarbonate, ammonium bicarbonate andsodium percarbonate.
 18. The composition of claim 13, wherein the sourceof hypochlorite is N-chloro-tosylamide.
 19. The composition of claim 13,further comprising an antimicrobial agent.
 20. The composition of claim19, wherein the antimicrobial agent is selected from the groupconsisting of biguanides, bisbiguanides, triguanides, and analoguesthereof.
 21. The composition of claim 19, wherein the antimicrobialagent is chlorhexidine.
 22. The therapeutic composition of claim 13,wherein the composition further comprises at least one compound selectedfrom the group consisting of an oxygen-producing compound, a poloxamer,a surfactant and a polyhydroxy acid.
 23. The therapeutic composition ofclaim 22, wherein the concentration of the oxygen-producing compound inthe composition is in the range of about 0.1% (v/v) to about 1% (v/v);the concentration of poloxamer in the composition is at least 4% (w/w);the concentration of surfactant in the composition is at least about0.1% (w/w); the concentration of polyhydroxy acid in the composition isat least about 0.2% (w/w); or, the concentration of surfactant in thecomposition is at least 0.1% (w/w).
 24. The composition of claim 13,wherein the pH of the composition is in the range of about 7.2 to about9.5.
 25. The therapeutic composition of claim 13, further comprising atleast one compound selected from the group consisting of chlorhexidine,polaxmer 237, lauramine oxide, and gluconolactone; wherein the chlorinesalt is selected sodium chloride or potassium chloride; wherein thesource of carbonate is selected from the group consisting of sodiumbicarbonate, potassium bicarbonate, calcium bicarbonate and ammoniumbicarbonate; wherein the source of hypochlorite is N-chlorotosylamide;and, wherein the pH of the composition is in the range of about 7.2 toabout 9.5
 26. A method of treating a patient having a wound, aninfection, inflammation of that is experiencing pain, comprisingadministering to the patient a therapeutic composition comprising: a) achloride salt; b) a source of bicarbonate; and c) a source ofhypochlorite; wherein the amount of the salt in the composition issufficient to render the composition hypertonic; and, wherein thecomposition is alkaline.
 27. The method of claim 26, wherein saidadministration potentiates wound healing, reduces the infection, reducesinflammation, promotes angiogenesis, or reduces pain.
 28. The method ofclaim 26, wherein: the concentration of the chloride salt in thecomposition is at least 200 mM; the concentration of the source ofcarbonate in the composition is at least 4.9M; and, the concentration ofthe source of hypochlorite is at least 0.5% (w/w).
 29. The method ofclaim 26, wherein the therapeutic composition further comprises at leastone compound selected from the group consisting of an oxygen-producingcompound, a poloxamer, a surfactant and a polyhydroxy acid.
 30. Amedical device comprising a therapeutic composition comprising: a) achloride salt; b) a source of bicarbonate; and c) a source ofhypochlorite; wherein the amount of the salt in the composition issufficient to render the composition hypertonic; and, wherein thecomposition is alkaline.
 31. The medical device of claim 30, wherein thedevice comprises a bandage, a dressing, a patch, a suture, a collagenplug, a catheter or a surgical implant,
 32. The method of claim 30,wherein: the concentration of the chloride salt in the composition is atleast 200 mM; the concentration of the source of carbonate in thecomposition is at least 4.9M; and, the concentration of the source ofhypochlorite is at least 0.5% (w/w).